Microbiocides

ABSTRACT

Compounds of the formula (I) in which the substituents are as defined in claim  1  are suitable for use as microbiocides. Formula (I), wherein X is oxygen or sulfur; A is a 5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur, or a phenyl ring; the heterocyclic ring or the phenyl being substituted by the groups R 6 , R 7  and R 8 ; R 6 , R 7  and R 8  are each, independently, hydrogen, halogen, cyano, nitro, C 1-4  alky, C 1-4  halogenalkyl, C 1-4  halogenalkoxy, C 1-4  alkoxy(C 1-4 )alkyl or C 1-4 halogenalkoxy(C 1-4 )alkyl, provided that at least one of R 6 , R 7  and R 8  is not hydrogen; B is a phenyl, naphthyl or quinolinyl group, which is substituted by one or more substituents R 9 .

This application is a 371 of International Application No. PCT/EP2007/004425 filed May 16, 2007, which claims priority to EP 06010224.1 filed May 18, 2006, the contents of which are incorporated herein by reference.

The present invention relates to novel microbiocidally active, in particular fungicidally active, cyclopropyl amides. It further relates to intermediates used in the preparation of these compounds, to compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.

N-[2-(2-pyridinyl)cycloalkyl]-carboxamide derivatives and their use as fungicides are described in WO 05/103006 and WO 05/103004. 2,6-Di-chloro-isonicotinic acid phenethyl-amide derivatives and their use as pesticides are described in JP-09-165-374.

It has been found that novel cyclopropyl amides have microbiocidal activity.

The present invention thus provides compounds of the formula I

wherein X is oxygen or sulfur; A is a 5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur, or a phenyl ring; the heterocyclic ring or the phenyl being substituted by the groups R₆, R₇ and R₈; R₆, R₇ and R₈ are each, independently, hydrogen, halogen, cyano, nitro, C₁₋₄alkyl, C₁₋₄ halogenalkyl, C₁₋₄ halogenalkoxy, C₁₋₄ alkoxy(C₁₋₄)alkyl or C₁₋₄ halogenalkoxy(C₁₋₄)alkyl, provided that at least one of R₆, R₇ and R₈ is not hydrogen;

R₁, R₂, R₃ and R₄ independently of each other stand for hydrogen, halogen, cyano, nitro, C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents R^(a), C₃-C₆cycloalkyl, which is unsubstituted or substituted by one or more substituents R^(a), C₂-C₆alkenyl, which is unsubstituted or substituted by one or more substituents R^(a) or C₂-C₆alkynyl, which is unsubstituted or substituted by one or more substituents R^(a);

each R^(a) independently of each other stand for halogen, cyano, nitro, C₁-C₆alkoxy, C₁-C₆halogenalkoxy, C₃-C₆cycloalkyl, C₁-C₆alkylthio, C₁-C₆halogenalkylthio or —C(R^(b))═N(OR^(c));

R^(b) is hydrogen or C₁-C₆alkyl;

R^(c) is C₁-C₆alkyl;

R₅ is hydrogen, C₁₋₄ alkyl, CH₂CH═CHR_(5a), CH₂C≡CR_(5b) or COR_(5c);

R_(5a) and R_(5b) are each, independently, hydrogen, C₁-C₆alkyl, C₁-C₆halogenalkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₇cycloalkyl, COOC₁-C₄alkyl, COOC₃-C₆alkenyl, COOC₃-C₆alkynyl or CN;

R_(5c) is hydrogen, C₁-C₆alkyl, C₁-C₆halogenalkyl, C₁-C₆alkoxy-C₁-C₆alkyl, C₁-C₆halogenalkoxy-C₁-C₆alkyl, C₁-C₆alkylthio, C₁-C₆halogenalkylthio, C₁-C₆alkoxy, C₁-C₆halogenalkoxy, C₃-C₆alkenyloxy, C₃-C₆halogenalkenyloxy, C₃-C₆alkynyloxy or C₃-C₆halogenalkynyloxy; B is a phenyl, naphthyl or quinolinyl group, which is substituted by one or more substituents R_(g); each substituent R₉ independently of each other stands for halogen, cyano, nitro, —C(R^(d))═N(OR^(e)) or a group -L-R¹; each R^(d) is independently of each other hydrogen or C₁-C₆alkyl; each R^(e) is independently of each other C₁-C₆alkyl; each L is independently of each other a bond, —O— or —S—; each R^(f) is independently of each other C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents R^(h), C₃-C₆cycloalkyl, which is unsubstituted or substituted by one or more substituents R^(h), C₆-C₁₄bicycloalkyl, which is unsubstituted or substituted by one or more substituents R^(h), C₂-C₆alkenyl, which is unsubstituted or substituted by one or more substituents R^(h), C₂-C₆alkynyl, which is unsubstituted or substituted by one or more substituents R^(h), phenyl, which is unsubstituted or substituted by one or more substituents R^(h), phenyl, which is unsubstituted or substituted by one or more substituents R^(h) or heteroaryl, which is unsubstituted or substituted by one or more substituents R^(h); each R^(h) is independently of each other halogen, cyano, nitro, C₁-C₆alkoxy, C₁-C₆halogenalkoxy, C₁-C₆alkylthio, C₁-C₆halogenalkylthio, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy or —C(R^(i))═N(OR^(k)); each R^(i) is independently of each other hydrogen or C₁-C₆alkyl; each R^(k) is independently of each other C₁-C₆alkyl; and tautomers/isomers/enantiomers of these compounds.

The alkyl groups occurring in the definitions of the substituents can be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl. Alkoxy, alkenyl and alkynyl radicals are derived from the alkyl radicals mentioned. The alkenyl and alkynyl groups can be mono- or di-unsaturated.

The cycloalkyl groups occurring in the definitions of the substituents are, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

The bicycloalkyl groups occurring in the definitions of the substituents are, depending on the ring size, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, bicyclo[3.2.2]nonane, bicyclo[4.2.2]decane, bicyclo[4.3.2]undecane, adamantane and the like.

Halogen is generally fluorine, chlorine, bromine or iodine, preferably fluorine, bromine or chlorine. This also applies, correspondingly, to halogen in combination with other meanings, such as halogenalkyl or halogenalkoxy.

Halogenalkyl groups preferably have a chain length of from 1 to 4 carbon atoms. Halogenalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl; preferably trichloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.

Suitable halogenalkenyl groups are alkenyl groups which are mono- or polysubstituted by halogen, halogen being fluorine, chlorine, bromine and iodine and in particular fluorine and chlorine, for example 2,2-difluoro-1-methylvinyl, 3-fluoropropenyl, 3-chloropropenyl, 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl and 4,4,4-trifluorobut-2-en-1-yl.

Suitable halogenalkynyl groups are, for example, alkynyl groups which are mono- or polysubstituted by halogen, halogen being bromine, iodine and in particular fluorine and chlorine, for example 3-fluoropropynyl, 3-chloropropynyl, 3-bromopropynyl, 3,3,3-trifluoro-propynyl and 4,4,4-trifluorobut-2-yn-1-yl.

Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy; preferably methoxy and ethoxy. Halogenalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy. Alkylthio is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio and ethylthio.

Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.

In the context of the present invention “substituted by one or more substituents” in the definition of substituents R₁, R₂, R₃, R₄ and R^(f), means typically, depending on the chemical structure of substituents R₁, R₂, R₃, R₄ and R^(f), monosubstituted to nine-times substituted, preferably monosubstituted to five-times substituted, more preferably mono-, double- or triple-substituted.

In the context of the present invention “substituted by one or more substituents” in the definition of substituent B, means typically, depending on the chemical structure of substituent B, monosubstituted to seven-times substituted, preferably monosubstituted to five-times substituted, more preferably mono-, double- or triple-substituted.

In the context of the present invention a “5- or 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur” preferably means pyrazolyl (especially pyrazol-4-yl), thiazolyl (especially thiazol-5-yl), pyrrolyl (especially pyrrol-3-yl), 1,2,3 triazolyl, oxazolyl (especially oxazol-5-yl), pyridyl (especially pyrid-3-yl) or 2,3 dihydro-[1,4]oxathiinyl (especially 2,3 dihydro-[1,4]oxathiin-5-yl).

In the context of the present invention “heteroaryl” is preferably understood to be an aromatic 5- or 6-membered heteroaryl group bonded via a carbon atom or an nitrogen atom, which group may be interrupted once by oxygen, once by sulfur and/or once, twice or three times by nitrogen. Said groups bonded via a carbon atom are, for example, pyrazol-3-yl, pyrazol-4-yl, 3-isoxazolyl, pyrrol-2-yl, pyrrol-3-yl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, 2-oxazolyl, 5-oxazolyl, 4-oxazolyl, 2-thiazolyl, 5-thiazolyl, 4-thiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-isothiazolyl, 1,2,3-triazol-4-yl, 1,2,3-triazol-2-yl, 1,2,4-triazol-3-yl, 1,2,3-oxadiazol-4-yl, 1,2,4-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,3-thiadiazol-4-yl, 1,2,4-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,5-thiadiazol-3-yl, 1,3,4-thiadiazol-2-yl, 2-pyridyl, 4-pyridyl, 3-pyridyl, 3-pyridazinyl, 3-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1,3,5-triazin-2-yl, 1,2,4-triazin-5-yl or 1,2,4-triazin-6-yl. Said groups bonded via a nitrogen atom are, for example, 1H-pyrrol-1-yl, 1H-pyrazol-1-yl, 1H-1,2,4-triazol-1-yl or 4H-1,2,4-triazol-4-yl.

All compounds of formula I occur in at least two different isomeric forms: I_(I) (cis) and I_(II) (trans):

The invention covers all those isomers and mixtures thereof.

The compounds of the formula I may occur in different tautomeric forms. For example, compounds of formula I, wherein X is oxygen and R₂ is hydrogen, exist in the tautomeric forms I_(III) and I_(IV):

The invention covers all those tautomeric forms and mixtures thereof.

In a preferred group of compounds A is a 5-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur; the heterocyclic ring being substituted by the groups R₆, R₇ and R₈.

Within said preferred group of compounds, further preferably A is A₁

in which R₁₆ is halogen, cyano, nitro, C₁-C₄alkyl, C₁-C₄halogenalkyl, C₁-C₄halogenalkoxy, C₁-C₄alkoxy-C₁-C₄alkyl or C₁-C₄halogenalkoxy-C₁-C₄alkyl; R₁₇ is C₁-C₄alkyl, C₁-C₄halogenalkyl, C₁-C₄halogenalkoxy, C₁-C₄alkoxy-C₁-C₄alkyl or C₁-C₄halogenalkoxy-C₁-C₄alkyl; and R₁₈ is hydrogen, halogen or cyano; or A is A₂

in which R₂₆ is halogen, cyano, nitro, C₁-C₄alkyl, C₁-C₄halogenalkyl, C₁-C₄halogenalkoxy, C₁-C₄alkoxy-C₁-C₄alkyl or C₁-C₄halogenalkoxy-C₁-C₄alkyl; and R₂₇ is C₁-C₄alkyl, C₁-C₄halogenalkyl, C₁-C₄halogenalkoxy, C₁-C₄alkoxy-C₁-C₄alkyl or C₁-C₄halogenalkoxy-C₁-C₄alkyl; or A is A₃

in which R₃₆ is halogen, cyano, nitro, C₁-C₄alkyl, C₁-C₄halogenalkyl, C₁-C₄halogenalkoxy, C₁-C₄alkoxy-C₁-C₄alkyl or C₁-C₄halogenalkoxy-C₁-C₄alkyl; R₃₇ is C₁-C₄alkyl, C₁-C₄halogenalkyl, C₁-C₄halogenalkoxy, C₁-C₄alkoxy-C₁-C₄alkyl or C₁-C₄halogenalkoxy-C₁-C₄alkyl; and R₃₈ is hydrogen, halogen or cyano; or A is A₄

in which R₄₆ and R₄₇ independently of one another are halogen, cyano, nitro, C₁-C₄alkyl, C₁-C₄halogenalkyl, C₁-C₄halogenalkoxy, C₁-C₄alkoxy-C₁-C₄alkyl or C₁-C₄halogenalkoxy-C₁-C₄alkyl.

Within said preferred group of compounds, further preferably A is A₁.

Within said preferred group of compounds, further preferably A is A₂.

Within said preferred group of compounds, further preferably A is A₃.

Within said preferred group of compounds, further preferably A is A₄.

In another preferred group of compounds A is a phenyl ring or a 6-membered heterocyclic ring containing one to three heteroatoms, each independently selected from oxygen, nitrogen and sulphur; the phenyl ring or the heterocyclic ring being substituted by the groups R₆, R₇ and R₈.

Within said preferred group of compounds, further preferably A is A₅

in which R₅₆ is halogen, C₁-C₄halogenalkyl, C₁-C₄halogenalkoxy or C₁-C₄halogenalkoxy-C₁-C₄alkyl; or A is A₆

in which R₆₆ is halogen, cyano, nitro, C₁-C₄alkyl, C₁-C₄halogenalkyl, C₁-C₄alkoxy-C₁-C₄alkyl or C₁-C₄halogenalkoxy-C₁-C₄alkyl; or A is A₇

in which R₇₆ is C₁-C₄alkyl or C₁-C₄halogenalkyl.

Within said preferred group of compounds, further preferably A is A₅.

Within said preferred group of compounds, further preferably A is A₆.

Within said preferred group of compounds, further preferably A is A₇.

In a particular preferred group of compounds A is A₁, wherein R₁₈ is hydrogen. In another particular preferred group of compounds A is A₁, wherein R₁₆ is C₁-C₄alkyl or C₁-C₄haloalkyl, preferably C₁-C₄haloalkyl; R₁₇ is C₁-C₄alkyl; and R₁₈ is hydrogen or halogen, preferably hydrogen.

In another particular preferred group of compounds A is A₂, wherein R₂₆ is C₁-C₄alkyl or C₁-C₄haloalkyl; and R₂₇ is C₁-C₄alkyl.

In yet another particular preferred group of compounds A is A₃, wherein R₃₆ is C₁-C₄alkyl or C₁-C₄haloalkyl; R₃₇ is C₁-C₄alkyl; and R₃₈ is hydrogen or halogen.

In yet another particular preferred group of compounds A is A₄, wherein R₄₆ is C₁-C₄alkyl or C₁-C₄haloalkyl; and R₄₇ is C₁-C₄alkyl.

In yet another particular preferred group of compounds A is A₄, wherein R₄₆ halomethyl, preferably R₄₆ is selected from CF₃, CF₂H and CFH₂; and R₄₇ is C₁-C₄alkyl.

In yet another particular preferred group of compounds A is A₅, wherein R₅₆ is halogen or C₁-C₄haloalkyl.

In yet another particular preferred group of compounds A is A₆, wherein R₆₆ is halogen or C₁-C₄haloalkyl.

In yet another particular preferred group of compounds A is A₇, wherein R₇₆ is C₁-C₄alkyl or C₁-C₄haloalkyl.

One embodiment of the invention is represented by compounds, wherein X is oxygen.

Another embodiment of the invention is represented by compounds, wherein X is sulfur.

Compounds, wherein X is oxygen are preferred.

In a preferred group of compounds R₅ is hydrogen.

In a preferred group of compounds R₁, R₂, R₃ and R₄ independently of each other stands for hydrogen, halogen, cyano or C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen, cyano, C₁-C₆alkoxy and ₁-C₆halogenalkoxy; more preferably R₁, R₂, R₃ and R₄ independently of each other stands for hydrogen, halogen, cyano or C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; most preferably R₁, R₂, R₃ and R₄ independently of each other stands for hydrogen, halogen, or C₁-C₆alkyl.

In a preferred group of compounds

R₁ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆halogenalkyl or C₁-C₆alkoxy-C₁-C₆alkyl;

R₂ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆halogenalkyl or C₁-C₆alkoxy-C₁-C₆alkyl;

R₃ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆halogenalkyl or C₁-C₆alkoxy-C₁-C₆alkyl; and R₄ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆halogenalkyl or C₁-C₆alkoxy-C₁-C₆alkyl.

Within said embodiment, preferably, R₁ is hydrogen, halogen or C₁-C₆alkyl; and R₂, R₃ and R₄ are each independently selected from hydrogen and C₁-C₆alkyl. Within said embodiment, more preferably R₃ and R₄ are hydrogen. In one embodiment R₂, R₃ and R₄ are hydrogen. In another embodiment, R₁, R₂, R₃ and R₄ are hydrogen.

One embodiment of the invention is represented by compounds, wherein B is a phenyl group, which is substituted by one or more substituents R₉.

Within said embodiment, preferably B is a phenyl group, which is substituted by one, two or three substituents R₉; more preferably B is a phenyl group, which is substituted by one or two substituents R₉.

Also preferably, B is a phenyl group, that is substituted by at least one substituent R₉ in the para-position.

In a preferred group of compounds each substituent R₉ independently of each other stands for halogen, —C(R^(d))═N(OR^(e)) or -L-R′; more preferably each substituent R₉ independently of each other stands for halogen or -L-R′. In a preferred group of compounds each L independently of each other is a bond or —O—. In a preferred group of compounds each substituent R^(f) independently of each other stands for C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; C₂-C₆alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.

Within said embodiment, further preferably B is B₁

in which R_(19a) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R_(19b) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R_(19c) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R_(19d) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R_(19e) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; provided that at least one of R_(19a), R_(19b), R_(19c), R_(19d) and R_(19e) is not hydrogen.

In one embodiment of the invention, R_(19b) and R_(19d) is hydrogen; and R_(19a), R_(19c) and R_(19e) independently of one another are selected from hydrogen, halogen, cyano, C₂-C₆alkynyl, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is substituted halogen; provided that at least one of R_(19a), R_(19c) and R_(19e) is not hydrogen.

Another embodiment of the invention is represented by compounds, wherein B is a naphthyl or quinolinyl group, which is substituted by one or more substituents R₉.

Another embodiment of the invention is represented by compounds, wherein B is a naphthyl group, which is substituted by one or more substituents R₉.

Within said embodiment, preferably B is a naphthyl group, which is substituted by one or two substituents R₉. Within said embodiment, in a preferred group of compounds each substituent R₆ independently of each other stands for halogen, —C(R^(d))═N(OR^(e)) or -L-R^(f); more preferably each substituent R₆ independently of each other stands for halogen or -L-R^(f). In a preferred group of compounds each L independently of each other is a bond or —O—. In a preferred group of compounds each substituent R^(f) independently of each other stands for C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; C₂-C₆alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.

Another embodiment of the invention is represented by compounds, wherein B is a quinolinyl group, which is substituted by one or more substituents R₉.

Within said embodiment, preferably B is a quinolinyl group, which is substituted by one or two substituents R₉. Within said embodiment, in a preferred group of compounds each substituent R₆ independently of each other stands for halogen, —C(R^(d))═N(OR^(e)) or -L-R^(f); more preferably each substituent R₆ independently of each other stands for halogen or -L-R^(f). In a preferred group of compounds each L independently of each other is a bond or —. In a preferred group of compounds each substituent R^(f) independently of each other stands for C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; C₂-C₆alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.

Compounds of formula I, wherein R₅ is hydrogen and X is oxygen, may be prepared by reacting a compound of formula II

in which B, R₁, R₂, R₃ and R₄ are as defined under formula I; with a compound of formula III A-C(═O)—R*  (III), in which A is as defined under formula I, and R* is halogen, hydroxy or C₁₋₆ alkoxy, preferably chloro, in the presence of a base, such as triethylamine, Hunig base, sodium bicarbonate, sodium carbonate, potassium carbonate, pyridine or quinoline, but preferably triethylamine, and in a solvent, such as diethylether, TBME, THF, dichloromethane, chloroform, DMF or NMP, for between 10 minutes and 48 hours, preferably 12 to 24 hours, and between 0° C. and reflux, preferably 20 to 25° C.

When R* is hydroxy, a coupling agent, such as benzotriazol-1-yloxytris(dimethylamino) phosphoniumhexafluorophosphate, bis-(2-oxo-3-oxazolidinyl)-phosphinic acid chloride (BOP-Cl), N,N′-dicyclohexylcarbodiimide (DCC) or 1,1′-carbonyl-diimidazole (CDI), may be used.

The Intermediates of the Formula II

in which B, R₁, R₂, R₃ and R₄ are as defined under formula I; are novel and were developed specifically for the preparation of the compounds of the formula I. Accordingly, they also form part of the subject-matter of the present invention.

In preferred intermediates of formula II, R₁, R₂, R₃ and R₄ independently of each other stands for hydrogen, halogen, cyano or C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen, cyano, C₁-C₆alkoxy and 1-C₆halogenalkoxy; more preferably R₁, R₂, R₃ and R₄ independently of each other stands for hydrogen, halogen, cyano or C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; most preferably R₁, R₂, R₃ and R₄ independently of each other stands for hydrogen, halogen, or C₁-C₆alkyl.

In a preferred group of intermediates of formula II, R₁ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆halogenalkyl or C₁-C₆alkoxy-C₁-C₆alkyl; R₂ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆halogenalkyl or C₁-C₆alkoxy-C₁-C₆alkyl; R₃ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆halogenalkyl or C₁-C₆alkoxy-C₁-C₆alkyl; and R₄ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆halogenalkyl or C₁-C₆alkoxy-C₁-C₆alkyl. Within said embodiment, preferably, R₁ is hydrogen, halogen or C₁-C₆alkyl; and R₂, R₃ and R₄ are each independently selected from hydrogen and C₁-C₆alkyl. Within said embodiment, more preferably R₃ and R₄ are hydrogen. In one embodiment R₂, R₃ and R₄ are hydrogen.

In preferred intermediates of formula II B is a phenyl group, which is substituted by one or more substituents R₉. Within said embodiment, preferably B is a phenyl group, which is substituted by one, two or three substituents R₉; more preferably B is a phenyl group, which is substituted by one or two substituents R₉. Also preferably, in intermediates of formula II B is a phenyl group, that is substituted by at least one substituent R₉ in the para-position.

In a preferred group of intermediates of formula II each substituent R₉ independently of each other stands for halogen, —C(R^(d))═N(OR^(e)) or -L-R^(f); more preferably each substituent R₉ independently of each other stands for halogen or -L-R^(f). In a preferred group of compounds each L independently of each other is a bond or —O—. In a preferred group of compounds each substituent R^(f) independently of each other stands for C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; C₂-C₆alkynyl, which is unsubstituted or substituted by one or more substituents selected from halogen and C₁-C₆alkoxy; or phenyl, which is unsubstituted or substituted by one or more halogens.

Within said embodiment, further preferably in intermediates of formula II B is B₁

in which R_(19a) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R_(19b) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R_(19c) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R_(19d) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; R_(19e) is hydrogen, halogen, cyano, C₁-C₆alkyl, C₂-C₆alkynyl, C₁-C₆alkoxy, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is unsubstituted or substituted by one or more halogens; provided that at least one of R_(19a), R_(19b), R_(19c), R_(19d) and R_(19e) is not hydrogen.

In one embodiment of the invention, in intermediates of formula II R_(19b) and R_(19d) is hydrogen; and R_(19a), R_(19g) and R_(19e) independently of one another are selected from hydrogen, halogen, cyano, C₂-C₆alkynyl, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is substituted halogen; provided that at least one of R_(19a), R_(19c) and R_(19e) is not hydrogen.

In another embodiment of the invention, in intermediates of formula II B is a naphthyl or quinolinyl group, which is substituted by one or more substituents R₉.

Intermediates of the formula II, in which B, R₁, R₂, R₃ and R₄ are as defined under formula I; may be prepared according to the following reaction schemes (scheme 1 and 2) or in analogy to those reaction schemes.

Intermediates of the Formula IIB

in which B is as defined under formula I (intermediates of formula II, in which R₁, R₂, R₃ and R₄ are hydrogen and B is as defined under formula I) may be prepared by reaction scheme 1.

Scheme 1, Route a (Cis-Selective Synthesis):

According to the procedure of Varinder K. Aggarwal et al, Organic Lett. 2001, Vol. 3, No. 17, 2785-2788, aldehydes of formula VIII, wherein B is as defined under formula I, are reacted with compounds of formula VII to give tosylhydrazones of formula VI, wherein B is as defined under formula I. These diazo-precursors of formula VI can be induced to react directly with N-vinylphthalimide (V) to afford phthalimides of the formula IV, wherein B is as defined under formula I, and following hydrazinolysis to afford the cis-2-arylcyclopropylamines of the formula IIB, wherein B is as defined under formula I.

The reactions are carried out at temperatures of between 0-50° C. in a convenient organic solvent such as methanol, ethanol, chloroform, dichloromethane or dioxane.

A range of metal catalysts such as the ones derived from copper, palladium, iron or rhodium can be used for the cyclopropanation reaction. The preferred catalyst is rhodium acetate which reacts with the sodium or lithium salt of the tosylhydrazone and N-vinylphthalimide (V) in the presence of a phase transfer catalyst such as benzyltriethylammonium chloride to give phthalimides of the formula IV.

The phthalimides of the formula IV are converted to the amines of formula IIB with hydrazine hydrate in a convenient solvent such as ethanol.

Scheme 1, Route b: Synthesis of Trans-Compounds

According to the procedure of A. Burger et al, J. Am. Soc., 70, 2198 (1948), J. of Med. Chem. 1962, 5, 1243-1265, 2-arylcyclopropylamines of the formula IIB, wherein B is as defined under formula I, can be prepared with a moderate trans-selectivity.

The cyclopropyl-esters trans/cis-(IX), wherein B is as defined under formula I, can be prepared by metal catalyzed cyclopropanation of an alkyl-diazoacetate of the formula N₂CHCO₂R, wherein R is C₁-C₆alkyl, with an olefin of the formula X, wherein B is as defined under formula I. Suitable solvents for this process include ether, CH₂Cl₂ and ClCH2CH₂Cl, preferably ether. Reaction temperatures range from room temperature to 60° C., preferably 40° C. Suitable catalysts for the cyclopropanation are Cu(acac)₂ or Pd(OAc)₂.

The 2-arylcyclopropylamines trans/cis-(IIB) are then prepared from the cyclopropyl-esters trans/cis-(IX) using a three-step sequence: basic hydrolysis of the ester (J. Valigarda et al, J. Chem. Soc. Perkin Trans. 1 1994), Curtius rearrangement, and finally hydrolysis of the isocyanate (P. A. S. Smith, Org. Reactions, III, 337 1946). The trans-2-arylcyclopropylamines of formula trans-(IIB) can be purified by recrystallisation of the corresponding D- and L-tartrates from aqueous 2-propanol according to known methods. 2-arylcyclopropylesters trans/cis-(IX) can selectively hydrolyzed by a modification of the method of H. M Walborsky and L. Plonsker, J. Am. Soc., 83, 2138 (1961).

Alternatively, cyclopropyl-esters trans/cis-(IX), wherein B is as defined under formula I, can be prepared by the reaction of diazomethane with an alkyl cinnamate of formula XI, wherein B is as defined under formula I, in the presence of Pd(OAc)₂ as described by U. Mende et al. THL No. 9, 629-632, 1975. Such cyclopropanations with diazomethane and chiral palladium(II) complexes are also described by Scott E. Denmark et al. J. Org. Chem. 1997, 62, 3375-3389. The trans-2-arylcyclopropylamines of formula trans-(IIB) can then be prepared from the cyclopropyl-esters trans/cis-(IX) as described above.

Intermediates of the Formula IIC

in which B is as defined under formula I and (II), R₁ is hydrogen, halogen, cyano, C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents R^(a), or C₃-C₆cycloalkyl, which is unsubstituted or substituted by one or more substituents R^(a), wherein each R^(a) independently of each other stand for halogen, cyano, nitro, C₁-C₆alkoxy, C₁-C₆halogenalkoxy, C₃-C₆cycloalkyl, C₁-C₆alkylthio or C₁-C₆halogenalkylthio; R₂ is hydrogen, cyano, nitro, C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents R^(a), or C₃-C₆cycloalkyl, which is unsubstituted or substituted by one or more substituents R^(a); wherein each R^(a) independently of each other stand for halogen, cyano, nitro, C₁-C₆alkoxy, C₁-C₆halogenalkoxy, C₃-C₆cycloalkyl, C₁-C₆alkylthio or C₁-C₆halogenalkylthio; R₃ and R₄ independently of each other stand for hydrogen, cyano, nitro, C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents R^(a), or C₃₋₆cycloalkyl, which is unsubstituted or substituted by one or more substituents R^(a); wherein each R^(a) independently of each other stand for halogen, cyano, nitro, C₁-C₆alkoxy, C₁-C₆halogenalkoxy, C₃-C₆cycloalkyl, C₁-C₆alkylthio or C₁-C₆halogenalkylthio; may be prepared by reaction scheme 2.

According to scheme 2, reaction of compounds of formula XVI, wherein R₁, R₃, R₄ and B are as defined under formula IIC, with alkyldiazoacetate derivatives of formula XV, wherein R₂ is as defined under formula IIC and R′ is C₁-C₆alkyl, and Vitamin B₁₂a as catalyst (Y. Chen and X. P. Zhang, J. Org. Chem. 2004, 69, 2431-2435), gives a diastereomeric mixture of cyclopropylcarboxylates of formula XIV, wherein R₁, R₂, R₃, R₄ and B are as defined under formula IIC. The diastereomers can be separated either chromatographically or, after saponification, by recrystallisation of the corresponding carboxylic acids of formula XIII, wherein R₁, R₂, R₃, R₄ and B are as defined under formula IIC. Curtius degradation to the BOC-protected amines of formula XII, wherein R₁, R₂, R₃, R₄ and B are as defined under formula IIC, and deprotection with hydrogen chloride produces the compounds of formula IIC in the form of hydrochlorides (see PCT/US2004/021505 and G. Haufe et al, J. Med. Chem. 2004, 47, 5860-5871). The cis and trans isomers of (XIV) or (XII) may be separated by chromatography.

The reactions are carried out at temperatures of between 0-100° C. in a convenient organic solvent such as methanol, ethanol, tert-butanol, trifluoroethanol, chloroform, dichloromethane or dioxane.

Other catalysts such as copper acetate can be used as an alternative to Vitamin B₁₂a for the cyclopropanation reaction.

The Curtius rearrangement of the carboxylic acids of formula XIII to the BOC-protected amines of formula XIII can be carried out using diphenylphosphoryl azide with a convenient base such as triethylamine followed by treatment with di-tert-butyl carbonate (D. Kim and S. M. Weinreb, J. Org. Chem. 1978, 43, 125-131). The BOC protecting group can be removed by sequential acid and base treatment.

Compounds of the formulae VIII, X, XI or XVI, all wherein B is a phenyl group, which is substituted by one or more substituents R₉, are known and are commercially available or can be prepared according to the above-mentioned references or according to methods known in the art.

Compounds of the formula III are known and partially commercially available. They can be prepared analogously as described, for example, in WO 00/09482, WO 02/38542, WO 04/018438, EP-0-589-301, WO 93/11117 and Arch. Pharm. Res. 2000, 23(4), 315-323.

The compounds of formula VII, V, and XV are known and are commercially available or can be prepared according to the above-mentioned references or according to methods known in the art.

Compounds of the formula XVII

wherein R₉ is as defined under formula I; n is 1, 2, 3, 4, 5, 6 or 7, preferably 1 or 2; R₁ is hydrogen, cyano, C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents R^(a), or C₃-C₆cycloalkyl, which is unsubstituted or substituted by one or more substituents R^(a), wherein each R^(a) independently of each other stand for halogen, cyano, nitro, C₁-C₆alkoxy, C₁-C₆halogenalkoxy, C₃-C₆cycloalkyl, C₁-C₆alkylthio or C₁-C₆halogenalkylthio; and R₃ and R₄ independently of each other stand for hydrogen, cyano, nitro, C₁-C₆alkyl, which is unsubstituted or substituted by one or more substituents R^(a), or C₃-C₆cycloalkyl, which is unsubstituted or substituted by one or more substituents R^(a); wherein each R^(a) independently of each other stand for halogen, cyano, nitro, C₁-C₆alkoxy, C₁-C₆halogenalkoxy, C₃-C₆cycloalkyl, C₁-C₆alkylthio or C₁-C₆halogenalkylthio; can be prepared according to reaction scheme 3 or in analogy to reaction scheme 3. Said compounds of formula XVII correspond to compounds of formula X or XVI, wherein B is a naphthyl group, which is substituted by one or more substituents R₉, with the exception of compounds according to formula XVI, wherein R₁ is halogen.

According to scheme 3, compounds of the formula XVII, wherein R₉, n, R₁, R₃ and R₄ are as defined above, can be prepared from compounds of formula XVIII, wherein R₉, n, R₁, R₃ and R₄ are as defined under formula XVII, or from compounds of formula XIX, wherein R₉, n, R₁, R₃ and R₄ are as defined under formula XVII, by alcohol-dehydration over KHSO₄ according to Charles C. Price et al. J Org Chem (1949), 14 111-117.

Compounds of the Formula XX

wherein Hal is F or Cl; can be prepared according to scheme 4. Compounds of formula XX form a sub-group of compounds of formula X or XVI.

Monohalogen-vinylnaphtalenes of formula XX, wherein Hal is F or Cl, can be prepared by a palladium-catalyzed vinylation of the naphthyl bromides of formula XXI, wherein Hal is F or Cl, using TBAF as activator and an inexpensive and non-toxic vinyl donor, such as 1,3,5,7-tetramethyl-1,3,5,7-tetravinylcyclotetrasiloxane, as published by Scott E. Denmark Organic Letters 2006 Vol. 8, No. 1 63-66.

Furthermore, the synthesis of 6-chloro-2-vinyinaphthalene is known, see J. Am. Chem. Soc., (1948), 70, 4265-4266.

Compounds of the formulae XIX, XVIII and XXI are known and are commercially available or can be prepared according to the above-mentioned references or according to methods known in the art.

Compounds of the formula XXII or XXIII

wherein R₉ is as defined under formula I; n is 1, 2, 3, 4, 5 or 6, preferably 1 or 2; and R₁, R₃ and R₄ are as defined under formula XVI, can be prepared according to reaction scheme 5 or in analogy to reaction scheme 5. Said compounds of formula XXII and XXIII correspond to compounds of formula X or XVI, wherein B is a quinolinyl group, which is substituted by one or more substituents R₉.

According to scheme 5, compounds of the formula XXII and XXIII, wherein R₉, n, R₁, R₃ and R₄ are as defined above, can be prepared from compounds of formula XXIV and XXV, respectively via a Wittig-reaction with compounds of formula XXVI, wherein R₂ is as defined under formula I.

Compounds of the formulae XXIV and XXV are known and are commercially available or can be prepared from known precursors according to methods known in the art. Especially, some monochloro-substituted 4-quinolinecarboxaldehydes and monochlorosubstituted 3-quinolinecarboxaldehydes are commercially available or known, for example, compounds XXIVa to XXIVj are registered under the following CAS-registry numbers.

Compounds according to Formula ID

wherein A and B are as defined in R₅ is C₁₋₄ alkyl, CH₂CH═CHR_(5a), CH₂C≡CR_(5b) or COR_(5c); R_(5a) and R_(5b) are each, independently, hydrogen, C₁-C₆alkyl, C₁-C₆halogenalkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₇cycloalkyl, COOC₁-C₄alkyl, COOC₃-C₆alkenyl, COOC₃-C₆alkynyl or CN; R_(5c) is hydrogen, C₁-C₆alkyl, C₁-C₆halogenalkyl, C₁-C₆alkoxy-C₁-C₆alkyl, C₁-C₆halogenalkoxy-C₁-C₆alkyl, C₁-C₆alkylthio, C₁-C₆halogenalkylthio, C₁-C₆alkoxy, C₁-C₆halogenalkoxy, C₃-C₆alkenyloxy, C₃-C₆halogenalkenyloxy, C₃-C₆alkynyloxy or C₃-C₆halogenalkynyloxy; may be prepared according to reaction scheme 6.

In compounds of formula XXVI B, R₁, R₂, R₃, R₄ and R₅ are as defined under formula IID.

Compounds of formula I, wherein X is sulfur, can be prepared from compounds of formula I, wherein X is oxygen, for example by reaction with P₂S₅ in an inert solvent, such as benzene, toluene, tetrahydrofurane, dioxane or mixtures thereof.

The compounds of the formula III are known and partially commercially available. They can be prepared analogously as described, for example, in WO 00/09482, WO 02/38542, WO 04/018438, EP-O-589-301, WO 93/11117 and Arch. Pharm. Res. 2000, 23(4), 315-323.

The compounds of formula VII, V, XI and XII are known and are commercially available or can be prepared according to the above-mentioned references or according to methods known in the art.

For preparing all further compounds of the formula I functionalized according to the definitions of A, B, X, R₁, R₂, R₃, R₄ and R₅, there are a large number of suitable known standard methods, such as alkylation, halogenation, acylation, amidation, oximation, oxidation and reduction. The choice of the preparation methods which are suitable are depending on the properties (reactivity) of the substituents in the intermediates.

The reactions to give compounds of the formula I are advantageously carried out in aprotic inert organic solvents. Such solvents are hydrocarbons such as benzene, toluene, xylene or cyclohexane, chlorinated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane or chlorobenzene, ethers such as diethyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran or dioxane, nitriles such as acetonitrile or propionitrile, amides such as N,N-dimethylformamide, diethylformamide or N-methylpyrrolidinone. The reaction temperatures are advantageously between −20° C. and +120° C. In general, the reactions are slightly exothermic and, as a rule, they can be carried out at room temperature. To shorten the reaction time, or else to start the reaction, the mixture may be heated briefly to the boiling point of the reaction mixture. The reaction times can also be shortened by adding a few drops of base as reaction catalyst. Suitable bases are, in particular, tertiary amines such as trimethylamine, triethylamine, quinuclidine, 1,4-diazabicyclo[2.2.2]octane, 1,5-diazabicyclo[4.3.0]non-5-ene or 1,5-diazabicyclo-[5.4.0]undec-7-ene. However, inorganic bases such as hydrides, e.g. sodium hydride or calcium hydride, hydroxides, e.g. sodium hydroxide or potassium hydroxide, carbonates such as sodium carbonate and potassium carbonate, or hydrogen carbonates such as potassium hydrogen carbonate and sodium hydrogen carbonate may also be used as bases. The bases can be used as such or else with catalytic amounts of a phase-transfer catalyst, for example a crown ether, in particular 18-crown-6, or a tetraalkylammonium salt.

The compounds of formula I can be isolated in the customary manner by concentrating and/or by evaporating the solvent and purified by recrystallization or trituration of the solid residue in solvents in which they are not readily soluble, such as ethers, aromatic hydrocarbons or chlorinated hydrocarbons.

The compounds I and, where appropriate, the tautomers thereof, can be present in the form of one of the isomers which are possible or as a mixture of these, for example in the form of pure isomers, such as antipodes and/or diastereomers, or as isomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure isomers and also to all isomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case.

Diastereomer mixtures or racemate mixtures of compounds I, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diasteromers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.

Enantiomer mixtures, such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high-performance liquid chromatography (HPLC) on acetyl cellulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is complexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the diastereomers, from which the desired enantiomer can be set free by the action of suitable agents, for example basic agents.

Pure diastereomers or enantiomers can be obtained according to the invention not only by separating suitable isomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials of a suitable stereochemistry.

It is advantageous to isolate or synthesize in each case the biologically more effective isomer, for example enantiomer or diastereomer, or isomer mixture, for example enantiomer mixture or diastereomer mixture, if the individual components have a different biological activity.

The compounds I and, where appropriate, the tautomers thereof, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form.

It has now been found that the compounds of formula I according to the invention have, for practical purposes, a very advantageous spectrum of activities for protecting useful plants against diseases that are caused by phytopathogenic microorganisms, such as fungi, bacteria or viruses.

The invention relates to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a compound of formula I is applied as active ingredient to the plants, to parts thereof or the locus thereof. The compounds of formula I according to the invention are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous useful plants. The compounds of formula I can be used to inhibit or destroy the diseases that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.

It is also possible to use compounds of formula I as dressing agents for the treatment of plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.

Furthermore the compounds of formula I according to the invention may be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage or in hygiene management.

The compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium, Septoria, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia). Additionally, they are also effective against the Ascomycetes classes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes classes (e.g. Phytophthora, Pythium, Plasmopara). Outstanding activity has been observed against powdery mildew (Erysiphe spp.). Furthermore, the novel compounds of formula I are effective against phytopathogenic bacteria and viruses (e.g. against Xanthomonas spp, Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus). Good activity has been observed against Asian soybean rust (Phakopsora pachyrhizi).

Within the scope of the invention, useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals.

The term “useful plants” is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.

The term “useful plants” is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.

The term “useful plants” is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called “pathogenesis-related proteins” (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.

The term “locus” of a useful plant as used herein is intended to embrace the place on which the useful plants are growing, where the plant propagation materials of the useful plants are sown or where the plant propagation materials of the useful plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.

The term “plant propagation material” is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably “plant propagation material” is understood to denote seeds.

The compounds of formula I can be used in unmodified form or, preferably, together with carriers and adjuvants conventionally employed in the art of formulation.

Therefore the invention also relates to compositions for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I and an inert carrier, and to a method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein a composition, comprising a compound of formula I as active ingredient and an inert carrier, is applied to the plants, to parts thereof or the locus thereof.

To this end compounds of formula I and inert carriers are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.

Suitable carriers and adjuvants can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.

The compounds of formula I or compositions, comprising a compound of formula I as active ingredient and an inert carrier, can be applied to the locus of the plant or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.

A preferred method of applying a compound of formula I, or a composition, comprising a compound of formula I as active ingredient and an inert carrier, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen. However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.

A formulation, i.e. a composition comprising the compound of formula I and, if desired, a solid or liquid adjuvant, is prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface-active compounds (surfactants).

The agrochemical formulations will usually contain from 0.1 to 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.

Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.

Advantageous rates of application are normally from 5 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a.i./ha, most preferably from 20 g to 600 g a.i./ha. When used as seed drenching agent, convenient rates of application are from 10 mg to 1 g of active substance per kg of seeds. The rate of application for the desired action can be determined by experiments. It depends for example on the type of action, the developmental stage of the useful plant, and on the application (location, timing, application method) and can, owing to these parameters, vary within wide limits.

Surprisingly, it has now been found that the compounds of formula I can also be used in methods of protecting crops of useful plants against attack by phytopathogenic organisms as well as the treatment of crops of useful plants infested by phytopathogenic organisms comprising administering a combination of glyphosate and at least one compound of formula I to the plant or locus thereof, wherein the plant is resistant or sensitive to glyphosate.

Said methods may provide unexpectedly improved control of diseases compared to using the compounds of formula I in the absence of glyphosate. Said methods may be effective at enhancing the control of disease by compounds of formula I. While the mixture of glyphosate and at least one compound of formula I may increase the disease spectrum controlled, at least in part, by the compound of formula I, an increase in the activity of the compound of formula I on disease species already known to be controlled to some degree by the compound of formula I can also be the effect observed.

Said methods are particularly effective against the phytopathogenic organisms of the kingdom Fungi, phylum Basidiomycot, class Uredinomycetes, subclass Urediniomycetidae and the order Uredinales (commonly referred to as rusts). Species of rusts having a particularly large impact on agriculture include those of the family Phakopsoraceae, particularly those of the genus Phakopsora, for example Phakopsora pachyrhizi, which is also referred to as Asian soybean rust, and those of the family Pucciniaceae, particularly those of the genus Puccinia such as Puccinia graminis, also known as stem rust or black rust, which is a problem disease in cereal crops and Puccinia recondita, also known as brown rust.

An embodiment of said method is a method of protecting crops of useful plants against attack by a phytopathogenic organism and/or the treatment of crops of useful plants infested by a phytopathogenic organism, said method comprising simultaneously applying glyphosate, including salts or esters thereof, and at least one compound of formula I, which has activity against the phytopathogenic organism to at least one member selected from the group consisting of the plant, a part of the plant and the locus of the plant.

Surprisingly, it has now been found that the compounds of formula I, or a pharmaceutical salt thereof, described above have also an advantageous spectrum of activity for the treatment and/or prevention of microbial infection in an animal.

“Animal” can be any animal, for example, insect, mammal, reptile, fish, amphibian, preferably mammal, most preferably human. “Treatment” means the use on an animal which has microbial infection in order to reduce or slow or stop the increase or spread of the infection, or to reduce the infection or to cure the infection. “Prevention” means the use on an animal which has no apparent signs of microbial infection in order to prevent any future infection, or to reduce or slow the increase or spread of any future infection.

According to the present invention there is provided the use of a compound of formula I in the manufacture of a medicament for use in the treatment and/or prevention of microbial infection in an animal. There is also provided the use of a compound of formula I as a pharmaceutical agent. There is also provided the use of a compound of formula I as an antimicrobial agent in the treatment of an animal. According to the present invention there is also provided a pharmaceutical composition comprising as an active ingredient a compound of formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. This composition can be used for the treatment and/or prevention of antimicrobial infection in an animal. This pharmaceutical composition can be in a form suitable for oral administration, such as tablet, lozenges, hard capsules, aqueous suspensions, oily suspensions, emulsions dispersible powders, dispersible granules, syrups and elixirs. Alternatively this pharmaceutical composition can be in a form suitable for topical application, such as a spray, a cream or lotion. Alternatively this pharmaceutical composition can be in a form suitable for parenteral administration, for example injection. Alternatively this pharmaceutical composition can be in inhalable form, such as an aerosol spray.

The compounds of formula I are effective against various microbial species able to cause a microbial infection in an animal. Examples of such microbial species are those causing Aspergillosis such as Aspergillus fumigatus, A. flavus, A. terrus, A. nidulans and A. niger; those causing Blastomycosis such as Blastomyces dermatitidis; those causing Candidiasis such as Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei and C. lusitaniae; those causing Coccidioidomycosis such as Coccidioides immitis; those causing Cryptococcosis such as Cryptococcus neoformans; those causing Histoplasmosis such as Histoplasma capsulatum and those causing Zygomycosis such as Absidia corymbifera, Rhizomucor pusillus and Rhizopus arrhizus. Further examples are Fusarium Spp such as Fusarium oxysporum and Fusarium solani and Scedosporium Spp such as Scedosporium apiospermum and Scedosporium prolificans. Still further examples are Microsporum Spp, Trichophyton Spp, Epidermophyton Spp, Mucor Spp, Sporothorix Spp, Phialophora Spp, Cladosporium Spp, Petriellidium spp, Paracoccidioides Spp and Histoplasma Spp.

The following non-limiting Examples illustrate the above-described invention in greater detail without limiting it.

PREPARATION EXAMPLES Example P1 Preparation of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2-(4-chlorophenyl)-cyclopropyl]-amide (Compound No. 1.001)

The crude amine Z1.001 from Example P4 was suspended in dichloromethane (10 ml) and triethylamine (250 mg, 2.5 mmol). To this suspension was added at 0° C. a solution of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (194 mg, 1.0 mmol) in dichloromethane (2 ml) and stirred for one hour. After removal of the solvent the residue was purified by flash chromatography over silica gel (eluant: hexane/ethyl acetate 1:9). Yield: 92 mg (28.2% of theory) of the cis-isomer of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2-(4-chlorophenyl)-cyclopropyl]-amide (compound no. 1.001) in form of a solid m.p. 127° C.

¹H NMR (400 MHz, CDCl₃): δ1.06-1.17 (m, 1H, CHH), 1.44 (q, 1H, CHH), 2.32-2.38 (q, 1H, CHAr), 3.23-3.29 (m, 1H, CHN), 3.73 (s, 3H, NCH₃), 6.08 (s, 1H, NH), 6.48-6.75 (t, 1H, CHF₂), 7.14-7.17 (d, 2H, Ar—H), 7.20-7.23 (d, 2H, Ar—H), 7.70 (s, 1H, Pyrazol-H). MS [M+H]⁺ 326/328.

Example P2 Preparation of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-amide (Compound No. 1.004)

A solution of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (0.105 g; 0.54 mmol) in dichloromethane (2 ml) was added dropwise to a stirred solution of the amine from example P5 (compound Z1.004; 2-(4-chlorophenyl)-2-fluoro-cyclopropylamine; 0.100 g; 0.54 mmol) and triethylamine (0.15 ml; 1.08 mmol) in dichloromethane (3 ml). The reaction mixture was stirred for 1 hr at ambient temperature then allowed to stand for 18 h. The reaction mixture was washed with 2M HCl (5 ml) and with saturated NaHCO₃ (5 ml) and then dried over MgSO₄. Evaporation of the solvent yielded 0.15 g 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-amide in the form of a yellow solid (81% of theory) as a 7:3 mixture of cis/trans isomers.

¹HNMR (400 MHz, CDCl₃): Cis isomer: 1.50δ (m; 1H): 1.92δ (ddd; 1H): 3.62δ (m; 1H): 3.85δ (s; 3H): 6.05δ (br-s; 1H): 6.60δ (t; 1H): 7.30δ-7.40δ (m; 4H): 7.80δ (s; 1H). Trans isomer: 1.57δ (m; 1H): 1.67δ (ddd; 1H): 3.32δ (m; 1H): 6.70δ (br-s; 1H): 6.85δ (t; 1H) 7.30δ-7.40δ (m; 4H): 7.95δ (s; 1H).

Example P3 Preparation of N-[(1R,2S)-2-(4-chlorophenyl)-2-fluoro-cyclopropyl]-2-trifluoromethyl-benzamide (Compound No. 6.004)

A solution of 2-trifluoromethylbenzoyl chloride (0.10 g; 0.54 mmol) in dichloromethane (2 ml) added dropwise to a stirred solution of the amine from example P5 (compound Z1.004; 2-(4-chlorophenyl)-2-fluoro-cyclopropylamine; 0.100 g; 0.54 mmol) and triethylamine (0.15 ml; 1.08 m) in dichloromethane (3 ml). Stirred for 1 hr at room temperature then allowed to stand for 18 hr. The white precipitate was filtered off, washed with 2M HCl, saturated NaHCO₃ and water and air dried giving the pure cis isomer. 0.065 g (34%).

¹HNMR (400 MHz, CDCl₃): 1.60δ (m; 1H): 1.97δ (ddd; 1H): 3.67δ (m; 1H): 5.40δ (br-s; 1H): 7.10δ-7.65δ (m; 8H). MH⁺ 358. MP 204-206⁰.

The dichloromethane soluble material consisted of a 1:1 mixture of cis/trans isomers.

Example P4 Preparation of (1R,2R)-2-(4-chloro-phenyl)-cyclopropylamine (Compound No. Z1.001) a) Preparation of 4-chlorobenzaldehyde tosyl hydrazone

To a stirred suspension of p-toluenesulfonyl hydrazide (5.0 g, 26.8 mmol) in methanol (20 ml) 4-chloro-benzaldehyde (3.3 g, 23.3 mol) was added dropwise. After 0.h hour the mixture was cooled to 0° C. and the product removed by filtration, washed with cold methanol (10 ml) and then crystallized from hot methanol to give 5.5 g (76.5% of theory) 4-chlorobenzaldehyde tosyl hydrazone in the form of a white solid.

¹H NMR (400 MHz, DMSO): δ 11.5 (S_(broad), 1H), 7.91 (s, 1H), 7.77 (d, 2H), 7.57 (d, 2H), 7.44 (d, 2H), 7.49 (d, 2H), 2.35 (s, 3H).

b) Preparation of 4-chlorobenzaldehyde tosyl hydrazone sodium salt

A 1 M sodium methoxyde solution was prepared by adding sodium (423 mg, 18.39 mmol) to anhydrous methanol (19 ml) with external cooling. Once all of the metal was dissolved, 4-chlorobenzaldehyde tosyl hydrazone (5.39 g, 17.51 mmol) was added and the mixture was stirred until the solid was dissolved. After stirring for a further 15 min at room temperature the methanol was removed under reduced pressure at room temperature. 5.73 g of 4-chlorobenzaldehyde tosyl hydrazone sodium salt was obtained in the form of a white powder (99% of theory).

c) Preparation of 2-[(1R,2R)-2-(4-chloro-phenyl)-cyclopropyl]-isoindole-1,3-dione

A mixture of 4-chlorobenzaldehyde tosyl hydrazone sodium salt (1.67 g, 5.05 mmol), benzyltriethylammoniumchloride (115 mg, 0.5 mmol), rhodium acetate (20 mg, 0.05 mmol) and N-vinylphtalimide (4.32 g, 25.0 mmol) in dry 1,4-dioxane (13 ml) was stirred for one day under nitrogen at room temperature. Water (35 ml) was added to the mixture and the aqueous phase was extracted three times with dichloromethane. The combined organic layers were dried over Na₂SO₄. Evaporation gave the crude material, which was purified by flash chromatography over silicagel (eluent: hexane/ethylacetate 1:1). To afford 392 mg (26.3% of theory) of 2-[2-(4-chloro-phenyl)-cyclopropyl]-isoindole-1,3-dione in the form of a solid.

¹H NMR (400 MHz, CDCl₃): δ 7.73-7.62 (m, 4H), 7.04-7.01 (m, 4H), 3.08 (td, 1H, CHN), 2.50 (q, 1H, CHPh), 2.19 (ddd, 1H, CHH), 1.63 (q, 1H, CHH).

MS [M+H]⁺ 298/300.

d) Preparation of (1R,2R)-2-(4-chloro-phenyl)-cyclopropylamine (Compound No. Z1.001)

A mixture of 2-[2-(4-chloro-phenyl)-cyclopropyl]-isoindole-1,3-dione (320 mg, 1.07 mmol) and hydrazine hydrate (0.5 ml) in ethanol (8 ml) was stirred for 0.5 hour at 50° C. The solution was evaporated under reduced pressure. The resulting amine (compound Z1.001) was used in example P1 without further purification.

Example P5 Preparation of 2-(4-chlorophenyl)-2-fluoro-cyclopropylamine (Compound No. Z1.004) a) Preparation of 2-(4-chlorophenyl)-2-fluoro-cyclopropane carboxylic acid ethyl ester

Vitamin B12a (1.00 g; 0.723 mmol) was dissolved in dry trifluoroethanol (70 ml) and 1-chloro-4-(1-fluoro-vinyl)-benzene (6.50 g; 41.5 mmol) and ethyl diazoacetate (6.30 g; 50 mmol; 90% purity) was added. The solution was stirred, under reflux, under nitrogen atmosphere for 18 h. After cooling the solvent was evaporated and the residue purified by flash chromatography using 9:1 hexane/ethyl acetate. 6.9 g of 2-(4-chlorophenyl)-2-fluoro-cyclopropane carboxylic acid ethyl ester was obtained in the form of an oil (81% of theory) as a 7:3 mixture of cis/trans isomers.

¹H NMR (400 MHz, CDCl3): cis isomer: 1.05δ (t; 3H): 1.82δ (ddd; 1H): 1.95δ (ddd; 1H): 2.57δ (ddd; 1H): 3.95δ (m; 2H): 7.206-7.42δ (m; 4H). Trans isomer: 1.30δ (t; 3H): 1.606 (ddd; 1H): 2.17δ (ddd; 1H): 2.30δ (ddd; 1H): 4.25δ (m; 2H): 7.206-7.42δ (m; 4H).

b) Preparation of 2-(4-chlorophenyl)-2-fluoro-cyclopropanecarboxylic acid

The ester from example P5a) (6.90 g; 28 mmol) was added dropwise to a stirred solution of KOH in methanol (0.956M; 300 ml; 0.28 m) with ice/water cooling. The solution was then stirred at room temperature for 18 h and concentrated under reduced pressure at room temperature. The residue was mixed with cold water and extracted with dichloromethane. The aqueous portion was acidified with concentrated HCl with ice cooling and extracted twice with dichloromethane. The extracts were dried (MgSO₄) and evaporated. 5.10 g of 2-(4-chlorophenyl)-2-fluoro-cyclopropanecarboxylic acid was obtained in the form of a yellow solid (85% of theory) as a 7:3 mixture of cis/trans isomers.

¹HNMR (400 MHz, CDCl₃): cis isomer: 1.856-2.00δ (m; 2H): 2.55δ (ddd; 1H); 7.206-7.406 (m; 4H). Trans isomer: 1.67δ (ddd; 1H): 2.12δ (ddd; 1H): 2.30δ (ddd; 1H): 7.206-7.406 (m; 4H).

c) Preparation of (2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-carbamic acid tert-butyl ester

The carboxylic acid from example P5b) (5.09 g; 23.7 mmol) was dissolved in a mixture of cyclohexane (150 ml) and tert-butanol (17.70 g; 0.237 m). Triethylamine (2.86 g; 0.0284 m) and diphenylphosphoryl azide (7.30 g; 0.0262 m) were added and the solution stirred under reflux under nitrogen for 18 h. After cooling, di-tert-butyl carbonate (7.86 g; 0.0359 m) was added and the mixture stirred under reflux for 2 h. After cooling the mixture was diluted with ethyl acetate (200 ml) and washed with 5% citric acid solution (50 ml) followed by saturated NaHCO₃ solution. The extract was dried (MgSO₄) and evaporated. The oily residue was triturated with pentane (50 ml) and the white solid filtered off and recrystallized from hexane. 4.3 g of (2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-carbamic acid tert-butyl ester was obtained in the from of a white solid (63% of theory) as a 7:3 mixture of cis/trans isomers.

¹HNMR (400 MHz, CDCl₃): cis isomer: 1.32δ (s; 9H): 1.42δ (m; 1H): 1.80δ (ddd; 1H): 3.30δ (m; 1H): 4.25δ (br-s; 1H): 7.306-7.40δ (m; 4H). Trans isomer: 1.40δ (m; 1H): 1.50δ (s; 9H): 2.97δ (m; 1H): 4.95δ (br-s; 1H): 7.306-7.40δ (m; 4H).

d) Preparation of 2-(4-chlorophenyl)-2-fluoro-cyclopropylamine (Compound No. Z1.004)

(2-(4-chlorophenyl)-2-fluoro-cyclopropyl)-carbamic acid tert-butyl ester from example P5c) (1.00 g; 3.5 mmol) was dissolved in methanol (10 ml) and a saturated solution of HCl in ethanol (10 ml) added. The solution was stirred at room temperature for 2 h then evaporated leaving a white solid. Water (50 ml) then added and mixture extracted twice with ethyl acetate. The aqueous phase was made alkaline with 2M NaOH and extracted twice with ethyl acetate. The extracts were dried (MgSO₄) and evaporated. 0.60 g of 2-(4-chlorophenyl)-2-fluoro-cyclopropylamine was obtained in the form of a yellow oil (92% of theory) as a 7:3 mixture of cis/trans isomers.

¹HNMR (400 MHz, CDCl₃): cis isomer: 1.15δ (ddd; 1H): 1.60δ (ddd; 1H): 3.10δ (ddd; 1H): 7.306-7.455 (m; 4H). Trans isomer: 1.27δ (ddd; 1H): 1.40δ (m; 1H): 2.57δ (ddd; 1H): 7.106-7.30δ (m; 4H).

Tables 1 to 8: Compounds of Formula IA

The invention is further illustrated by the preferred individual compounds of formula (IA) listed below in Tables 1 to 8. Characterising data is given in Table 18.

Each of Tables 1 to 8, which follow the Table Y below, comprises 274 compounds of the formula (IA) in which R₁, R₂, R₃, R₄, R_(9a), R_(9b) and R_(9c) have the values given in Table Y and A has the value given in the relevant Table 1 to 8. Thus Table 1 corresponds to Table Y when Y is 1 and A has the value given under the Table 1 heading, Table 2 corresponds to Table Y when Y is 2 and A has the value given under the Table 2 heading, and so on for Tables 3 to 8.

TABLE Y Cpd No. R₁ R₂ R₃ R₄ R_(9a) R_(9b) R_(9c) Y.001 H H H H 4-Cl H H Y.002 CH₃ H H H 4-Cl H H Y.003 CH₂CH₃ H H H 4-Cl H H Y.004 F H H H 4-Cl H H Y.005 CN H H H 4-Cl H H Y.006 H CH₃ H H 4-Cl H H Y.007 CH₃ CH₃ H H 4-Cl H H Y.008 CH₂CH₃ CH₃ H H 4-Cl H H Y.009 F CH₃ H H 4-Cl H H Y.010 CN CH₃ H H 4-Cl H H Y.011 H CH₂CH₃ H H 4-Cl H H Y.012 CH₃ CH₂CH₃ H H 4-Cl H H Y.013 F CH₂CH₃ H H 4-Cl H H Y.014 CN CH₂CH₃ H H 4-Cl H H Y.015 H H F H 4-Cl H H Y.016 CH₃ H F H 4-Cl H H Y.017 F H F H 4-Cl H H Y.018 H CH₃ F H 4-Cl H H Y.019 CH₃ CH₃ F H 4-Cl H H Y.020 F CH₃ F H 4-Cl H H Y.021 H H F F 4-Cl H H Y.022 CH₃ H F F 4-Cl H H Y.023 F H F F 4-Cl H H Y.024 H CH₃ F F 4-Cl H H Y.025 CH₃ CH₃ F F 4-Cl H H Y.026 F CH₃ F F 4-Cl H H Y.027 H H H H 4-CF₃ H H Y.028 CH₃ H H H 4-CF₃ H H Y.029 CH₂CH₃ H H H 4-CF₃ H H Y.030 F H H H 4-CF₃ H H Y.031 CN H H H 4-CF₃ H H Y.032 H CH₃ H H 4-CF₃ H H Y.033 CH₃ CH₃ H H 4-CF₃ H H Y.034 CH₂CH₃ CH₃ H H 4-CF₃ H H Y.035 F CH₃ H H 4-CF₃ H H Y.036 CN CH₃ H H 4-CF₃ H H Y.037 H CH₂CH₃ H H 4-CF₃ H H Y.038 CH₃ CH₂CH₃ H H 4-CF₃ H H Y.039 F CH₂CH₃ H H 4-CF₃ H H Y.040 CN CH₂CH₃ H H 4-CF₃ H H Y.041 H H F H 4-CF₃ H H Y.042 CH₃ H F H 4-CF₃ H H Y.043 F H F H 4-CF₃ H H Y.044 H CH₃ F H 4-CF₃ H H Y.045 CH₃ CH₃ F H 4-CF₃ H H Y.046 F CH₃ F H 4-CF₃ H H Y.047 H H F F 4-CF₃ H H Y.048 CH₃ H F F 4-CF₃ H H Y.049 F H F F 4-CF₃ H H Y.050 H CH₃ F F 4-CF₃ H H Y.051 CH₃ CH₃ F F 4-CF₃ H H Y.052 F CH₃ F F 4-CF₃ H H Y.053 H H H H 4-OCF₃ H H Y.054 CH₃ H H H 4-OCF₃ H H Y.055 CH₂CH₃ H H H 4-OCF₃ H H Y.056 F H H H 4-OCF₃ H H Y.057 CN H H H 4-OCF₃ H H Y.058 H CH₃ H H 4-OCF₃ H H Y.059 CH₃ CH₃ H H 4-OCF₃ H H Y.060 CH₂CH₃ CH₃ H H 4-OCF₃ H H Y.061 F CH₃ H H 4-OCF₃ H H Y.062 CN CH₃ H H 4-OCF₃ H H Y.063 H CH₂CH₃ H H 4-OCF₃ H H Y.064 CH₃ CH₂CH₃ H H 4-OCF₃ H H Y.065 F CH₂CH₃ H H 4-OCF₃ H H Y.066 CN CH₂CH₃ H H 4-OCF₃ H H Y.067 H H F H 4-OCF₃ H H Y.068 CH₃ H F H 4-OCF₃ H H Y.069 F H F H 4-OCF₃ H H Y.070 H CH₃ F H 4-OCF₃ H H Y.071 CH₃ CH₃ F H 4-OCF₃ H H Y.072 F CH₃ F H 4-OCF₃ H H Y.073 H H F F 4-OCF₃ H H Y.074 CH₃ H F F 4-OCF₃ H H Y.075 F H F F 4-OCF₃ H H Y.076 H CH₃ F F 4-OCF₃ H H Y.077 CH₃ CH₃ F F 4-OCF₃ H H Y.078 F CH₃ F F 4-OCF₃ H H Y.079 H H H H 4-F H H Y.080 F H H H 4-F H H Y.081 H CH₃ H H 4-F H H Y.082 F CH₃ H H 4-F H H Y.083 H CH₂CH₃ H H 4-F H H Y.084 H H F H 4-F H H Y.085 F H F H 4-F H H Y.086 H CH₃ F H 4-F H H Y.087 F CH₃ F H 4-F H H Y.088 H H F F 4-F H H Y.089 F H F F 4-F H H Y.090 F CH₃ F F 4-F H H Y.091 H H H H 4-p-Cl-phenyl H H Y.092 CH₃ H H H 4-p-Cl-phenyl H H Y.093 CH₂CH₃ H H H 4-p-Cl-phenyl H H Y.094 F H H H 4-p-Cl-phenyl H H Y.095 CN H H H 4-p-Cl-phenyl H H Y.096 H CH₃ H H 4-p-Cl-phenyl H H Y.097 CH₃ CH₃ H H 4-p-Cl-phenyl H H Y.098 CH₂CH₃ CH₃ H H 4-p-Cl-phenyl H H Y.099 F CH₃ H H 4-p-Cl-phenyl H H Y.100 CN CH₃ H H 4-p-Cl-phenyl H H Y.101 H CH₂CH₃ H H 4-p-Cl-phenyl H H Y.102 CH₃ CH₂CH₃ H H 4-p-Cl-phenyl H H Y.103 F CH₂CH₃ H H 4-p-Cl-phenyl H H Y.104 CN CH₂CH₃ H H 4-p-Cl-phenyl H H Y.105 H H F H 4-p-Cl-phenyl H H Y.106 CH₃ H F H 4-p-Cl-phenyl H H Y.107 F H F H 4-p-Cl-phenyl H H Y.108 H CH₃ F H 4-p-Cl-phenyl H H Y.109 CH₃ CH₃ F H 4-p-Cl-phenyl H H Y.110 F CH₃ F H 4-p-Cl-phenyl H H Y.111 H H F F 4-p-Cl-phenyl H H Y.112 CH₃ H F F 4-p-Cl-phenyl H H Y.113 F H F F 4-p-Cl-phenyl H H Y.114 H CH₃ F F 4-p-Cl-phenyl H H Y.115 CH₃ CH₃ F F 4-p-Cl-phenyl H H Y.116 F CH₃ F F 4-p-Cl-phenyl H H Y.117 H H H H 4-C≡CC(CH₃)₃ H H Y.118 CH₃ H H H 4-C≡CC(CH₃)₃ H H Y.119 CH₂CH₃ H H H 4-C≡CC(CH₃)₃ H H Y.120 F H H H 4-C≡CC(CH₃)₃ H H Y.121 CN H H H 4-C≡CC(CH₃)₃ H H Y.122 H CH₃ H H 4-C≡CC(CH₃)₃ H H Y.123 CH₃ CH₃ H H 4-C≡CC(CH₃)₃ H H Y.124 CH₂CH₃ CH₃ H H 4-C≡CC(CH₃)₃ H H Y.125 F CH₃ H H 4-C≡CC(CH₃)₃ H H Y.126 CN CH₃ H H 4-C≡CC(CH₃)₃ H H Y.127 H CH₂CH₃ H H 4-C≡CC(CH₃)₃ H H Y.128 CH₃ CH₂CH₃ H H 4-C≡CC(CH₃)₃ H H Y.129 F CH₂CH₃ H H 4-C≡CC(CH₃)₃ H H Y.130 CN CH₂CH₃ H H 4-C≡CC(CH₃)₃ H H Y.131 H H F H 4-C≡CC(CH₃)₃ H H Y.132 H CH₃ F H 4-C≡CC(CH₃)₃ H H Y.133 CH₃ CH₃ F H 4-C≡CC(CH₃)₃ H H Y.134 F CH₃ F H 4-C≡CC(CH₃)₃ H H Y.135 H H F F 4-C≡CC(CH₃)₃ H H Y.136 CH₃ H F F 4-C≡CC(CH₃)₃ H H Y.137 F H F F 4-C≡CC(CH₃)₃ H H Y.138 H CH₃ F F 4-C≡CC(CH₃)₃ H H Y.139 CH₃ CH₃ F F 4-C≡CC(CH₃)₃ H H Y.140 F CH₃ F F 4-C≡CC(CH₃)₃ H H Y.141 H H H H 4-C≡CC(CH₃)₃ H H Y.142 CH₃ H H H 4-C≡CC(CH₃)₃ H H Y.143 H H H H 4-Cl 2-Cl H Y.144 CH₃ H H H 4-Cl 2-Cl H Y.145 CH₂CH₃ H H H 4-Cl 2-Cl H Y.146 F H H H 4-Cl 2-Cl H Y.147 CN H H H 4-Cl 2-Cl H Y.148 H CH₃ H H 4-Cl 2-Cl H Y.149 CH₃ CH₃ H H 4-Cl 2-Cl H Y.150 CH₂CH₃ CH₃ H H 4-Cl 2-Cl H Y.151 F CH₃ H H 4-Cl 2-Cl H Y.152 CN CH₃ H H 4-Cl 2-Cl H Y.153 H CH₂CH₃ H H 4-Cl 2-Cl H Y.154 CH₃ CH₂CH₃ H H 4-Cl 2-Cl H Y.155 F CH₂CH₃ H H 4-Cl 2-Cl H Y.156 CN CH₂CH₃ H H 4-Cl 2-Cl H Y.157 H H F H 4-Cl 2-Cl H Y.158 CH₃ H F H 4-Cl 2-Cl H Y.159 F H F H 4-Cl 2-Cl H Y.160 H CH₃ F H 4-Cl 2-Cl H Y.161 CH₃ CH₃ F H 4-Cl 2-Cl H Y.162 F CH₃ F H 4-Cl 2-Cl H Y.163 H H F F 4-Cl 2-Cl H Y.164 CH₃ H F F 4-Cl 2-Cl H Y.165 F H F F 4-Cl 2-Cl H Y.166 H CH₃ F F 4-Cl 2-Cl H Y.167 CH₃ CH₃ F F 4-Cl 2-Cl H Y.168 F CH₃ F F 4-Cl 2-Cl H Y.169 H H H H 4-F 2-F H Y.170 CH₃ H H H 4-F 2-F H Y.171 CH₂CH₃ H H H 4-F 2-F H Y.172 F H H H 4-F 2-F H Y.173 CN H H H 4-F 2-F H Y.174 H CH₃ H H 4-F 2-F H Y.175 CH₃ CH₃ H H 4-F 2-F H Y.176 CH₂CH₃ CH₃ H H 4-F 2-F H Y.177 F CH₃ H H 4-F 2-F H Y.178 CN CH₃ H H 4-F 2-F H Y.179 H CH₂CH₃ H H 4-F 2-F H Y.180 CH₃ CH₂CH₃ H H 4-F 2-F H Y.181 F CH₂CH₃ H H 4-F 2-F H Y.182 CN CH₂CH₃ H H 4-F 2-F H Y.183 H H F H 4-F 2-F H Y.184 CH₃ H F H 4-F 2-F H Y.185 F H F H 4-F 2-F H Y.186 H CH₃ F H 4-F 2-F H Y.187 CH₃ CH₃ F H 4-F 2-F H Y.188 F CH₃ F H 4-F 2-F H Y.189 H H F F 4-F 2-F H Y.190 CH₃ H F F 4-F 2-F H Y.191 F H F F 4-F 2-F H Y.192 H CH₃ F F 4-F 2-F H Y.193 CH₃ CH₃ F F 4-F 2-F H Y.194 F CH₃ F F 4-F 2-F H Y.195 H H H H 4-Cl 2-F H Y.196 CH₃ H H H 4-Cl 2-F H Y.197 CH₂CH₃ H H H 4-Cl 2-F H Y.198 F H H H 4-Cl 2-F H Y.199 CN H H H 4-Cl 2-F H Y.200 H CH₃ H H 4-Cl 2-F H Y.201 CH₃ CH₃ H H 4-Cl 2-F H Y.202 CH₂CH₃ CH₃ H H 4-Cl 2-F H Y.203 F CH₃ H H 4-Cl 2-F H Y.204 CN CH₃ H H 4-Cl 2-F H Y.205 H CH₂CH₃ H H 4-Cl 2-F H Y.206 CH₃ CH₂CH₃ H H 4-Cl 2-F H Y.207 F CH₂CH₃ H H 4-Cl 2-F H Y.208 CN CH₂CH₃ H H 4-Cl 2-F H Y.209 H H F H 4-Cl 2-F H Y.210 CH₃ H F H 4-Cl 2-F H Y.211 F H F H 4-Cl 2-F H Y.212 H CH₃ F H 4-Cl 2-F H Y.213 CH₃ CH₃ F H 4-Cl 2-F H Y.214 F CH₃ F H 4-Cl 2-F H Y.215 H H F F 4-Cl 2-F H Y.216 CH₃ H F F 4-Cl 2-F H Y.217 F H F F 4-Cl 2-F H Y.218 H CH₃ F F 4-Cl 2-F H Y.219 CH₃ CH₃ F F 4-Cl 2-F H Y.220 F CH₃ F F 4-Cl 2-F H Y.221 H H H H 4-F 2-Cl H Y.222 H H H H 2-Cl H H Y.223 CH₂CH₃ H H H 4-F 2-Cl H Y.224 F H H H 4-F 2-Cl H Y.225 CN H H H 4-F 2-Cl H Y.226 H CH₃ H H 4-F 2-Cl H Y.227 CH₃ CH₃ H H 4-F 2-Cl H Y.228 CH₂CH₃ CH₃ H H 4-F 2-Cl H Y.229 F CH₃ H H 4-F 2-Cl H Y.230 CN CH₃ H H 4-F 2-Cl H Y.231 H CH₂CH₃ H H 4-F 2-Cl H Y.232 CH₃ CH₂CH₃ H H 4-F 2-Cl H Y.233 F CH₂CH₃ H H 4-F 2-Cl H Y.234 CN CH₂CH₃ H H 4-F 2-Cl H Y.235 H H F H 4-F 2-Cl H Y.236 CH₃ H F H 4-F 2-Cl H Y.237 F H F H 4-F 2-Cl H Y.238 H CH₃ F H 4-F 2-Cl H Y.239 CH₃ CH₃ F H 4-F 2-Cl H Y.240 F CH₃ F H 4-F 2-Cl H Y.241 H H F F 4-F 2-Cl H Y.242 CH₃ H F F 4-F 2-Cl H Y.243 F H F F 4-F 2-Cl H Y.244 H CH₃ F F 4-F 2-Cl H Y.245 CH₃ CH₃ F F 4-F 2-Cl H Y.246 F CH₃ F F 4-F 2-Cl H Y.247 H H H H 4-p-Cl-phenyl 2-Cl H Y.248 F H H H 4-p-Cl-phenyl 2-Cl H Y.249 H CH₃ H H 4-p-Cl-phenyl 2-Cl H Y.250 F CH₃ H H 4-p-Cl-phenyl 2-Cl H Y.251 H H F H 4-p-Cl-phenyl 2-Cl H Y.252 F H F H 4-p-Cl-phenyl 2-Cl H Y.253 H CH₃ F H 4-p-Cl-phenyl 2-Cl H Y.254 F CH₃ F H 4-p-Cl-phenyl 2-Cl H Y.255 H H F F 4-p-Cl-phenyl 2-Cl H Y.256 H CH₃ F F 4-p-Cl-phenyl 2-Cl H Y.257 H H H H 4-Br 2-Cl H Y.258 H H H H 4-Br 2-Cl 6-Cl Y.259 H H H H 4-Cl 2-Cl 6-Cl Y.260 H H H H 4-p-CF₃-phenyl 2-Cl 6-Cl Y.261 H H H H 4-p-CF₃-phenyl 2-Cl H Y.262 H H H H 4-(3′,4′-Cl₂)-phenyl 2-Cl H Y.263 H H H H 4-(3′,4′-Cl₂)-phenyl 2-Cl 6-Cl Y.264 H H H H 4-p-Cl-phenyl 2-Cl 6-Cl Y.265 H H H H 4-(CH₃) 2-Cl 6-(CH₃) Y.266 H H H H 4-(CH₃) 2-CH₃ 6-(CH₃) Y.267 H H H H 4-C≡CC(CH₃)₃ 2-Cl H Y.268 H H H H 4-C≡CC(CH₃)₃ 2-Cl 6-Cl Y.269 H H H H 4-C≡CCH(CH₂)₂ 2-Cl H Y.270 H H H H 4-C≡CCH(CH₂)₂ 2-Cl 6-Cl Y.271 H H H H 4-CH═N—OCH₃ 2-Cl H Y.272 H H H H 4-CH═N—OCH₃ 2-Cl 6-Cl Y.273 H H H H 4-C(CH₃)═N—OCH₃ 2-Cl H Y.274 H H H H 4-C(CH₃)═N—OCH₃ 2-Cl 6-Cl

Table 1 provides 274 compounds of formula (IA), wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and R₁, R₂, R₃, R₄, R_(9a), R_(9b) and R_(9c) are as defined in Table Y. For example, compound 1.001 has the following structure:

Table 2 provides 274 compounds of formula (IA) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and R₁, R₂, R₃, R₄, R_(9a), R_(9b) and R_(9c) are as defined in Table Y.

Table 3 provides 274 compounds of formula (IA) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and R₁, R₂, R₃, R₄, R_(9a), R_(9b) and R_(9c) are as defined in Table Y.

Table 4 provides 274 compounds of formula (IA) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and R₁, R₂, R₃, R₄, R_(9a), R_(9b) and R_(9c) are as defined in Table Y.

Table 5 provides 274 compounds of formula (IA) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and R₁, R₂, R₃, R₄, R_(9a), R_(9b) and R_(9c) are as defined in Table Y.

Table 6 provides 274 compounds of formula (IA) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and R₁, R₂, R₃, R₄, R_(9a), R_(9b) and R_(9c) are as defined in Table Y.

Table 7 provides 274 compounds of formula (IA) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and R₁, R₂, R₃, R₄, R_(9a), R_(9b) and R_(9c) are as defined in Table Y.

Table 8 provides 274 compounds of formula (IA) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and R₁, R₂, R₃, R₄, R_(9a), R_(9b) and R_(9c) are as defined in Table Y. Tables 9 to 16: Compounds of Formula IB

The invention is further illustrated by the preferred individual compounds of formula (IB) listed below in Tables 9 to 16. Characterising data is given in Table 18.

Each of Tables 9 to 16, which follow the Table W below, comprises 872 compounds of the formula (IB) in which B, R₁, R₂, R₃ and R₄ have the values given in Table W and A has the value given in the relevant Table 9 to 16. Thus Table 9 corresponds to Table W when W is 9 and A has the value given under the Table 9 heading, Table 10 corresponds to Table W when W is 10 and A has the value given under the Table 10 heading, and so on for Tables 11 to 16.

In Table W the group B stands for the group B₁, B₂, B₃ or B₄:

TABLE W

Compound No. B R₁ R₂ R₃ R₄ R_(9a) R_(9b) W.001 B₁ H H H H 2-Cl H W.002 B₁ CH₃ H H H 2-Cl H W.003 B₁ CH₂CH₃ H H H 2-Cl H W.004 B₁ F H H H 2-Cl H W.005 B₁ CN H H H 2-Cl H W.006 B₁ H CH₃ H H 2-Cl H W.007 B₁ CH₃ CH₃ H H 2-Cl H W.008 B₁ CH₂CH₃ CH₃ H H 2-Cl H W.009 B₁ F CH₃ H H 2-Cl H W.010 B₁ CN CH₃ H H 2-Cl H W.011 B₁ H CH₂CH₃ H H 2-Cl H W.012 B₁ CH₃ CH₂CH₃ H H 2-Cl H W.013 B₁ F CH₂CH₃ H H 2-Cl H W.014 B₁ CN CH₂CH₃ H H 2-Cl H W.015 B₁ H H F H 2-Cl H W.016 B₁ CH₃ H F H 2-Cl H W.017 B₁ F H F H 2-Cl H W.018 B₁ H CH₃ F H 2-Cl H W.019 B₁ CH₃ CH₃ F H 2-Cl H W.020 B₁ F CH₃ F H 2-Cl H W.021 B₁ H H F F 2-Cl H W.022 B₁ H H CH₃ CH₃ 2-Cl H W.023 B₁ F H CH₃ CH₃ 2-Cl H W.024 B₁ H CH₃ CH₃ CH₃ 2-Cl H W.025 B₁ CH₃ CH₃ CH₃ CH₃ 2-Cl H W.026 B₁ F CH₃ CH₃ CH₃ 2-Cl H W.027 B₁ H H H H 4-Cl H W.028 B₁ CH₃ H H H 4-Cl H W.029 B₁ CH₂CH₃ H H H 4-Cl H W.030 B₁ F H H H 4-Cl H W.031 B₁ CN H H H 4-Cl H W.032 B₁ H CH₃ H H 4-Cl H W.033 B₁ CH₃ CH₃ H H 4-Cl H W.034 B₁ CH₂CH₃ CH₃ H H 4-Cl H W.035 B₁ F CH₃ H H 4-Cl H W.036 B₁ CN CH₃ H H 4-Cl H W.037 B₁ H CH₂CH₃ H H 4-Cl H W.038 B₁ CH₃ CH₂CH₃ H H 4-Cl H W.039 B₁ F CH₂CH₃ H H 4-Cl H W.040 B₁ CN CH₂CH₃ H H 4-Cl H W.041 B₁ H H F H 4-Cl H W.042 B₁ CH₃ H F H 4-Cl H W.043 B₁ F H F H 4-Cl H W.044 B₁ H CH₃ F H 4-Cl H W.045 B₁ CH₃ CH₃ F H 4-Cl H W.046 B₁ F CH₃ F H 4-Cl H W.047 B₁ H H F F 4-Cl H W.048 B₁ H H CH₃ CH₃ 4-Cl H W.049 B₁ F H CH₃ CH₃ 4-Cl H W.050 B₁ H CH₃ CH₃ CH₃ 4-Cl H W.051 B₁ CH₃ CH₃ CH₃ CH₃ 4-Cl H W.052 B₁ F CH₃ CH₃ CH₃ 4-Cl H W.053 B₁ H H H H 5-Cl H W.054 B₁ CH₃ H H H 5-Cl H W.055 B₁ CH₂CH₃ H H H 5-Cl H W.056 B₁ F H H H 5-Cl H W.057 B₁ CN H H H 5-Cl H W.058 B₁ H CH₃ H H 5-Cl H W.059 B₁ CH₃ CH₃ H H 5-Cl H W.060 B₁ CH₂CH₃ CH₃ H H 5-Cl H W.061 B₁ F CH₃ H H 5-Cl H W.062 B₁ CN CH₃ H H 5-Cl H W.063 B₁ H CH₂CH₃ H H 5-Cl H W.064 B₁ CH₃ CH₂CH₃ H H 5-Cl H W.065 B₁ F CH₂CH₃ H H 5-Cl H W.066 B₁ CN CH₂CH₃ H H 5-Cl H W.067 B₁ H H F H 5-Cl H W.068 B₁ CH₃ H F H 5-Cl H W.069 B₁ F H F H 5-Cl H W.070 B₁ H CH₃ F H 5-Cl H W.071 B₁ CH₃ CH₃ F H 5-Cl H W.072 B₁ F CH₃ F H 5-Cl H W.073 B₁ H H F F 5-Cl H W.074 B₁ H H CH₃ CH₃ 5-Cl H W.075 B₁ F H CH₃ CH₃ 5-Cl H W.076 B₁ H CH₃ CH₃ CH₃ 5-Cl H W.077 B₁ CH₃ CH₃ CH₃ CH₃ 5-Cl H W.078 B₁ F CH₃ CH₃ CH₃ 5-Cl H W.079 B₁ H H H H 6-Cl H W.080 B₁ CH₃ H H H 6-Cl H W.081 B₁ CH₂CH₃ H H H 6-Cl H W.082 B₁ F H H H 6-Cl H W.083 B₁ CN H H H 6-Cl H W.084 B₁ H CH₃ H H 6-Cl H W.085 B₁ CH₃ CH₃ H H 6-Cl H W.086 B₁ CH₂CH₃ CH₃ H H 6-Cl H W.087 B₁ F CH₃ H H 6-Cl H W.088 B₁ CN CH₃ H H 6-Cl H W.089 B₁ H CH₂CH₃ H H 6-Cl H W.090 B₁ CH₃ CH₂CH₃ H H 6-Cl H W.091 B₁ F CH₂CH₃ H H 6-Cl H W.092 B₁ CN CH₂CH₃ H H 6-Cl H W.093 B₁ H H F H 6-Cl H W.094 B₁ CH₃ H F H 6-Cl H W.095 B₁ F H F H 6-Cl H W.096 B₁ H CH₃ F H 6-Cl H W.097 B₁ CH₃ CH₃ F H 6-Cl H W.098 B₁ F CH₃ F H 6-Cl H W.099 B₁ H H F F 6-Cl H W.100 B₁ H H CH₃ CH₃ 6-Cl H W.101 B₁ F H CH₃ CH₃ 6-Cl H W.102 B₁ H CH₃ CH₃ CH₃ 6-Cl H W.103 B₁ CH₃ CH₃ CH₃ CH₃ 6-Cl H W.104 B₁ F CH₃ CH₃ CH₃ 6-Cl H W.105 B₁ H H H H 8-Cl H W.106 B₁ CH₃ H H H 8-Cl H W.107 B₁ CH₂CH₃ H H H 8-Cl H W.108 B₁ F H H H 8-Cl H W.109 B₁ CN H H H 8-Cl H W.110 B₁ H CH₃ H H 8-Cl H W.111 B₁ CH₃ CH₃ H H 8-Cl H W.112 B₁ CH₂CH₃ CH₃ H H 8-Cl H W.113 B₁ F CH₃ H H 8-Cl H W.114 B₁ CN CH₃ H H 8-Cl H W.115 B₁ H CH₂CH₃ H H 8-Cl H W.116 B₁ CH₃ CH₂CH₃ H H 8-Cl H W.117 B₁ F CH₂CH₃ H H 8-Cl H W.118 B₁ CN CH₂CH₃ H H 8-Cl H W.119 B₁ H H F H 8-Cl H W.120 B₁ CH₃ H F H 8-Cl H W.121 B₁ F H F H 8-Cl H W.122 B₁ H CH₃ F H 8-Cl H W.123 B₁ CH₃ CH₃ F H 8-Cl H W.124 B₁ F CH₃ F H 8-Cl H W.125 B₁ H H F F 8-Cl H W.126 B₁ H H CH₃ CH₃ 8-Cl H W.127 B₁ F H CH₃ CH₃ 8-Cl H W.128 B₁ H CH₃ CH₃ CH₃ 8-Cl H W.129 B₁ CH₃ CH₃ CH₃ CH₃ 8-Cl H W.130 B₁ F CH₃ CH₃ CH₃ 8-Cl H W.131 B₁ H H H H 2-p-Cl-phenyl H W.132 B₁ CH₃ H H H 2-p-Cl-phenyl H W.133 B₁ CH₂CH₃ H H H 2-p-Cl-phenyl H W.134 B₁ F H H H 2-p-Cl-phenyl H W.135 B₁ CN H H H 2-p-Cl-phenyl H W.136 B₁ H CH₃ H H 2-p-Cl-phenyl H W.137 B₁ CH₃ CH₃ H H 2-p-Cl-phenyl H W.138 B₁ CH₂CH₃ CH₃ H H 2-p-Cl-phenyl H W.139 B₁ F CH₃ H H 2-p-Cl-phenyl H W.140 B₁ CN CH₃ H H 2-p-Cl-phenyl H W.141 B₁ H CH₂CH₃ H H 2-p-Cl-phenyl H W.142 B₁ CH₃ CH₂CH₃ H H 2-p-Cl-phenyl H W.143 B₁ F CH₂CH₃ H H 2-p-Cl-phenyl H W.144 B₁ CN CH₂CH₃ H H 2-p-Cl-phenyl H W.145 B₁ H H F H 2-p-Cl-phenyl H W.146 B₁ CH₃ H F H 2-p-Cl-phenyl H W.147 B₁ F H F H 2-p-Cl-phenyl H W.148 B₁ H CH₃ F H 2-p-Cl-phenyl H W.149 B₁ CH₃ CH₃ F H 2-p-Cl-phenyl H W.150 B₁ F CH₃ F H 2-p-Cl-phenyl H W.151 B₁ H H F F 2-p-Cl-phenyl H W.152 B₁ H H CH₃ CH₃ 2-p-Cl-phenyl H W.153 B₁ F H CH₃ CH₃ 2-p-Cl-phenyl H W.154 B₁ H CH₃ CH₃ CH₃ 2-p-Cl-phenyl H W.155 B₁ CH₃ CH₃ CH₃ CH₃ 2-p-Cl-phenyl H W.156 B₁ F CH₃ CH₃ CH₃ 2-p-Cl-phenyl H W.157 B₁ H H H H 4-p-Cl-phenyl H W.158 B₁ CH₃ H H H 4-p-Cl-phenyl H W.159 B₁ CH₂CH₃ H H H 4-p-Cl-phenyl H W.160 B₁ F H H H 4-p-Cl-phenyl H W.161 B₁ CN H H H 4-p-Cl-phenyl H W.162 B₁ H CH₃ H H 4-p-Cl-phenyl H W.163 B₁ CH₃ CH₃ H H 4-p-Cl-phenyl H W.164 B₁ CH₂CH₃ CH₃ H H 4-p-Cl-phenyl H W.165 B₁ F CH₃ H H 4-p-Cl-phenyl H W.166 B₁ CN CH₃ H H 4-p-Cl-phenyl H W.167 B₁ H CH₂CH₃ H H 4-p-Cl-phenyl H W.168 B₁ CH₃ CH₂CH₃ H H 4-p-Cl-phenyl H W.169 B₁ F CH₂CH₃ H H 4-p-Cl-phenyl H W.170 B₁ CN CH₂CH₃ H H 4-p-Cl-phenyl H W.171 B₁ H H F H 4-p-Cl-phenyl H W.172 B₁ CH₃ H F H 4-p-Cl-phenyl H W.173 B₁ F H F H 4-p-Cl-phenyl H W.174 B₁ H CH₃ F H 4-p-Cl-phenyl H W.175 B₁ CH₃ CH₃ F H 4-p-Cl-phenyl H W.176 B₁ F CH₃ F H 4-p-Cl-phenyl H W.177 B₁ H H F F 4-p-Cl-phenyl H W.178 B₁ H H CH₃ CH₃ 4-p-Cl-phenyl H W.179 B₁ F H CH₃ CH₃ 4-p-Cl-phenyl H W.180 B₁ H CH₃ CH₃ CH₃ 4-p-Cl-phenyl H W.181 B₁ CH₃ CH₃ CH₃ CH₃ 4-p-Cl-phenyl H W.182 B₁ F CH₃ CH₃ CH₃ 4-p-Cl-phenyl H W.183 B₁ H H H H 8-p-Cl-phenyl H W.184 B₁ CH₃ H H H 8-p-Cl-phenyl H W.185 B₁ CH₂CH₃ H H H 8-p-Cl-phenyl H W.186 B₁ F H H H 8-p-Cl-phenyl H W.187 B₁ CN H H H 8-p-Cl-phenyl H W.188 B₁ H CH₃ H H 8-p-Cl-phenyl H W.189 B₁ CH₃ CH₃ H H 8-p-Cl-phenyl H W.190 B₁ CH₂CH₃ CH₃ H H 8-p-Cl-phenyl H W.191 B₁ F CH₃ H H 8-p-Cl-phenyl H W.192 B₁ CN CH₃ H H 8-p-Cl-phenyl H W.193 B₁ H CH₂CH₃ H H 8-p-Cl-phenyl H W.194 B₁ CH₃ CH₂CH₃ H H 8-p-Cl-phenyl H W.195 B₁ F CH₂CH₃ H H 8-p-Cl-phenyl H W.196 B₁ CN CH₂CH₃ H H 8-p-Cl-phenyl H W.197 B₁ H H F H 8-p-Cl-phenyl H W.198 B₁ CH₃ H F H 8-p-Cl-phenyl H W.199 B₁ F H F H 8-p-Cl-phenyl H W.200 B₁ H CH₃ F H 8-p-Cl-phenyl H W.201 B₁ CH₃ CH₃ F H 8-p-Cl-phenyl H W.202 B₁ F CH₃ F H 8-p-Cl-phenyl H W.203 B₁ H H F F 8-p-Cl-phenyl H W.204 B₁ H H CH₃ CH₃ 8-p-Cl-phenyl H W.205 B₁ F H CH₃ CH₃ 8-p-Cl-phenyl H W.206 B₁ H CH₃ CH₃ CH₃ 8-p-Cl-phenyl H W.207 B₁ CH₃ CH₃ CH₃ CH₃ 8-p-Cl-phenyl H W.208 B₁ F CH₃ CH₃ CH₃ 8-p-Cl-phenyl H W.209 B₁ H H H H 2-Cl 4-Cl W.210 B₁ CH₃ H H H 2-Cl 4-Cl W.211 B₁ CH₂CH₃ H H H 2-Cl 4-Cl W.212 B₁ F H H H 2-Cl 4-Cl W.213 B₁ CN H H H 2-Cl 4-Cl W.214 B₁ H CH₃ H H 2-Cl 4-Cl W.215 B₁ CH₃ CH₃ H H 2-Cl 4-Cl W.216 B₁ CH₂CH₃ CH₃ H H 2-Cl 4-Cl W.217 B₁ F CH₃ H H 2-Cl 4-Cl W.218 B₁ CN CH₃ H H 2-Cl 4-Cl W.219 B₁ H CH₂CH₃ H H 2-Cl 4-Cl W.220 B₁ CH₃ CH₂CH₃ H H 2-Cl 4-Cl W.221 B₁ F CH₂CH₃ H H 2-Cl 4-Cl W.222 B₁ CN CH₂CH₃ H H 2-Cl 4-Cl W.223 B₁ H H F H 2-Cl 4-Cl W.224 B₁ CH₃ H F H 2-Cl 4-Cl W.225 B₁ F H F H 2-Cl 4-Cl W.226 B₁ H CH₃ F H 2-Cl 4-Cl W.227 B₁ CH₃ CH₃ F H 2-Cl 4-Cl W.228 B₁ F CH₃ F H 2-Cl 4-Cl W.229 B₁ H H F F 2-Cl 4-Cl W.230 B₁ H H CH₃ CH₃ 2-Cl 4-Cl W.231 B₁ F H CH₃ CH₃ 2-Cl 4-Cl W.232 B₁ H CH₃ CH₃ CH₃ 2-Cl 4-Cl W.233 B₁ CH₃ CH₃ CH₃ CH₃ 2-Cl 4-Cl W.234 B₁ F CH₃ CH₃ CH₃ 2-Cl 4-Cl W.235 B₁ H H H H 2-p-Cl-phenyl 4-Cl W.236 B₁ CH₃ H H H 2-p-Cl-phenyl 4-Cl W.237 B₁ CH₂CH₃ H H H 2-p-Cl-phenyl 4-Cl W.238 B₁ F H H H 2-p-Cl-phenyl 4-Cl W.239 B₁ CN H H H 2-p-Cl-phenyl 4-Cl W.240 B₁ H CH₃ H H 2-p-Cl-phenyl 4-Cl W.241 B₁ CH₃ CH₃ H H 2-p-Cl-phenyl 4-Cl W.242 B₁ CH₂CH₃ CH₃ H H 2-p-Cl-phenyl 4-Cl W.243 B₁ F CH₃ H H 2-p-Cl-phenyl 4-Cl W.244 B₁ CN CH₃ H H 2-p-Cl-phenyl 4-Cl W.245 B₁ H CH₂CH₃ H H 2-p-Cl-phenyl 4-Cl W.246 B₁ CH₃ CH₂CH₃ H H 2-p-Cl-phenyl 4-Cl W.247 B₁ F CH₂CH₃ H H 2-p-Cl-phenyl 4-Cl W.248 B₁ CN CH₂CH₃ H H 2-p-Cl-phenyl 4-Cl W.249 B₁ H H F H 2-p-Cl-phenyl 4-Cl W.250 B₁ CH₃ H F H 2-p-Cl-phenyl 4-Cl W.251 B₁ F H F H 2-p-Cl-phenyl 4-Cl W.252 B₁ H CH₃ F H 2-p-Cl-phenyl 4-Cl W.253 B₁ CH₃ CH₃ F H 2-p-Cl-phenyl 4-Cl 254 B₁ F CH₃ F H 2-p-Cl-phenyl 4-Cl W.255 B₁ H H F F 2-p-Cl-phenyl 4-Cl W.256 B₁ H H CH₃ CH₃ 2-p-Cl-phenyl 4-Cl W.257 B₂ H H H H 6-Cl H W.258 B₂ CH₃ H H H 6-Cl H W.259 B₂ CH₂CH₃ H H H 6-Cl H W.260 B₂ F H H H 6-Cl H W.261 B₂ CN H H H 6-Cl H W.262 B₂ H CH₃ H H 6-Cl H W.263 B₂ CH₃ CH₃ H H 6-Cl H W.264 B₂ CH₂CH₃ CH₃ H H 6-Cl H W.265 B₂ F CH₃ H H 6-Cl H W.266 B₂ CN CH₃ H H 6-Cl H W.267 B₂ H CH₂CH₃ H H 6-Cl H W.268 B₂ CH₃ CH₂CH₃ H H 6-Cl H W.269 B₂ F CH₂CH₃ H H 6-Cl H W.270 B₂ CN CH₂CH₃ H H 6-Cl H W.271 B₂ H H F H 6-Cl H W.272 B₂ CH₃ H F H 6-Cl H W.273 B₂ F H F H 6-Cl H W.274 B₂ H CH₃ F H 6-Cl H W.275 B₂ CH₃ CH₃ F H 6-Cl H W.276 B₂ F CH₃ F H 6-Cl H W.277 B₂ H H F F 6-Cl H W.278 B₂ H H CH₃ CH₃ 6-Cl H W.279 B₂ F H CH₃ CH₃ 6-Cl H W.280 B₂ H CH₃ CH₃ CH₃ 6-Cl H W.281 B₂ CH₃ CH₃ CH₃ CH₃ 6-Cl H W.282 B₂ F CH₃ CH₃ CH₃ 6-Cl H W.283 B₂ H H H H 6-OCF₃ H W.284 B₂ CH₃ H H H 6-OCF₃ H W.285 B₂ CH₂CH₃ H H H 6-OCF₃ H W.286 B₂ F H H H 6-OCF₃ H W.287 B₂ CN H H H 6-OCF₃ H W.288 B₂ H CH₃ H H 6-OCF₃ H W.289 B₂ CH₃ CH₃ H H 6-OCF₃ H W.290 B₂ CH₂CH₃ CH₃ H H 6-OCF₃ H W.291 B₂ F CH₃ H H 6-OCF₃ H W.292 B₂ CN CH₃ H H 6-OCF₃ H W.293 B₂ H CH₂CH₃ H H 6-OCF₃ H W.294 B₂ CH₃ CH₂CH₃ H H 6-OCF₃ H W.295 B₂ F CH₂CH₃ H H 6-OCF₃ H W.296 B₂ CN CH₂CH₃ H H 6-OCF₃ H W.297 B₂ H H F H 6-OCF₃ H W.298 B₂ CH₃ H F H 6-OCF₃ H W.299 B₂ F H F H 6-OCF₃ H W.300 B₂ H CH₃ F H 6-OCF₃ H W.301 B₂ CH₃ CH₃ F H 6-OCF₃ H W.302 B₂ F CH₃ F H 6-OCF₃ H W.303 B₂ H H F F 6-OCF₃ H W.304 B₂ H H CH₃ CH₃ 6-OCF₃ H W.305 B₂ F H CH₃ CH₃ 6-OCF₃ H W.306 B₂ H CH₃ CH₃ CH₃ 6-OCF₃ H W.307 B₂ CH₃ CH₃ CH₃ CH₃ 6-OCF₃ H W.308 B₂ F CH₃ CH₃ CH₃ 6-OCF₃ H W.309 B₂ H H H H 6-CF₃ H W.310 B₂ CH₃ H H H 6-CF₃ H W.311 B₂ CH₂CH₃ H H H 6-CF₃ H W.312 B₂ F H H H 6-CF₃ H W.313 B₂ CN H H H 6-CF₃ H W.314 B₂ H CH₃ H H 6-CF₃ H W.315 B₂ CH₃ CH₃ H H 6-CF₃ H W.316 B₂ CH₂CH₃ CH₃ H H 6-CF₃ H W.317 B₂ F CH₃ H H 6-CF₃ H W.318 B₂ CN CH₃ H H 6-CF₃ H W.319 B₂ H CH₂CH₃ H H 6-CF₃ H W.320 B₂ CH₃ CH₂CH₃ H H 6-CF₃ H W.321 B₂ F CH₂CH₃ H H 6-CF₃ H W.322 B₂ CN CH₂CH₃ H H 6-CF₃ H W.323 B₂ H H F H 6-CF₃ H W.324 B₂ CH₃ H F H 6-CF₃ H W.325 B₂ F H F H 6-CF₃ H W.326 B₂ H CH₃ F H 6-CF₃ H W.327 B₂ CH₃ CH₃ F H 6-CF₃ H W.328 B₂ F CH₃ F H 6-CF₃ H W.329 B₂ H H F F 6-CF₃ H W.330 B₂ H H CH₃ CH₃ 6-CF₃ H W.331 B₂ F H CH₃ CH₃ 6-CF₃ H W.332 B₂ H CH₃ CH₃ CH₃ 6-CF₃ H W.333 B₂ CH₃ CH₃ CH₃ CH₃ 6-CF₃ H W.334 B₂ F CH₃ CH₃ CH₃ 6-CF₃ H W.335 B₂ H H H H 6-p-Cl-phenyl H W.336 B₂ CH₃ H H H 6-p-Cl-phenyl H W.337 B₂ CH₂CH₃ H H H 6-p-Cl-phenyl H W.338 B₂ F H H H 6-p-Cl-phenyl H W.339 B₂ CN H H H 6-p-Cl-phenyl H W.340 B₂ H CH₃ H H 6-p-Cl-phenyl H W.341 B₂ CH₃ CH₃ H H 6-p-Cl-phenyl H W.342 B₂ CH₂CH₃ CH₃ H H 6-p-Cl-phenyl H W.343 B₂ F CH₃ H H 6-p-Cl-phenyl H W.344 B₂ CN CH₃ H H 6-p-Cl-phenyl H W.345 B₂ H CH₂CH₃ H H 6-p-Cl-phenyl H W.346 B₂ CH₃ CH₂CH₃ H H 6-p-Cl-phenyl H W.347 B₂ F CH₂CH₃ H H 6-p-Cl-phenyl H W.348 B₂ CN CH₂CH₃ H H 6-p-Cl-phenyl H W.349 B₂ H H F H 6-p-Cl-phenyl H W.350 B₂ CH₃ H F H 6-p-Cl-phenyl H W.351 B₂ F H F H 6-p-Cl-phenyl H W.352 B₂ H CH₃ F H 6-p-Cl-phenyl H W.353 B₂ CH₃ CH₃ F H 6-p-Cl-phenyl H W.354 B₂ F CH₃ F H 6-p-Cl-phenyl H W.355 B₂ H H F F 6-p-Cl-phenyl H W.356 B₂ H H CH₃ CH₃ 6-p-Cl-phenyl H W.357 B₂ F H CH₃ CH₃ 6-p-Cl-phenyl H W.358 B₂ H CH₃ CH₃ CH₃ 6-p-Cl-phenyl H W.359 B₂ CH₃ CH₃ CH₃ CH₃ 6-p-Cl-phenyl H W.360 B₂ F CH₃ CH₃ CH₃ 6-p-Cl-phenyl H W.361 B₃ H H H H 2-Cl H W.362 B₃ CH₃ H H H 2-Cl H W.363 B₃ CH₂CH₃ H H H 2-Cl H W.364 B₃ F H H H 2-Cl H W.365 B₃ CN H H H 2-Cl H W.366 B₃ H CH₃ H H 2-Cl H W.367 B₃ CH₃ CH₃ H H 2-Cl H W.368 B₃ CH₂CH₃ CH₃ H H 2-Cl H W.369 B₃ F CH₃ H H 2-Cl H W.370 B₃ CN CH₃ H H 2-Cl H W.371 B₃ H CH₂CH₃ H H 2-Cl H W.372 B₃ CH₃ CH₂CH₃ H H 2-Cl H W.373 B₃ F CH₂CH₃ H H 2-Cl H W.374 B₃ CN CH₂CH₃ H H 2-Cl H W.375 B₃ H H F H 2-Cl H W.376 B₃ CH₃ H F H 2-Cl H W.377 B₃ F H F H 2-Cl H W.378 B₃ H CH₃ F H 2-Cl H W.379 B₃ CH₃ CH₃ F H 2-Cl H W.380 B₃ F CH₃ F H 2-Cl H W.381 B₃ H H F F 2-Cl H W.382 B₃ H H CH₃ CH₃ 2-Cl H W.383 B₃ F H CH₃ CH₃ 2-Cl H W.384 B₃ H CH₃ CH₃ CH₃ 2-Cl H W.385 B₃ CH₃ CH₃ CH₃ CH₃ 2-Cl H W.386 B₃ F CH₃ CH₃ CH₃ 2-Cl H W.387 B₃ H H H H 3-Cl H W.388 B₃ CH₃ H H H 3-Cl H W.389 B₃ CH₂CH₃ H H H 3-Cl H W.390 B₃ F H H H 3-Cl H W.391 B₃ CN H H H 3-Cl H W.392 B₃ H CH₃ H H 3-Cl H W.393 B₃ CH₃ CH₃ H H 3-Cl H W.394 B₃ CH₂CH₃ CH₃ H H 3-Cl H W.395 B₃ F CH₃ H H 3-Cl H W.396 B₃ CN CH₃ H H 3-Cl H W.397 B₃ H CH₂CH₃ H H 3-Cl H W.398 B₃ CH₃ CH₂CH₃ H H 3-Cl H W.399 B₃ F CH₂CH₃ H H 3-Cl H W.400 B₃ CN CH₂CH₃ H H 3-Cl H W.401 B₃ H H F H 3-Cl H W.402 B₃ CH₃ H F H 3-Cl H W.403 B₃ F H F H 3-Cl H W.404 B₃ H CH₃ F H 3-Cl H W.405 B₃ CH₃ CH₃ F H 3-Cl H W.406 B₃ F CH₃ F H 3-Cl H W.407 B₃ H H F F 3-Cl H W.408 B₃ H H CH₃ CH₃ 3-Cl H W.409 B₃ F H CH₃ CH₃ 3-Cl H W.410 B₃ H CH₃ CH₃ CH₃ 3-Cl H W.411 B₃ CH₃ CH₃ CH₃ CH₃ 3-Cl H W.412 B₃ F CH₃ CH₃ CH₃ 3-Cl H W.413 B₃ H H H H 6-Cl H W.414 B₃ CH₃ H H H 6-Cl H W.415 B₃ CH₂CH₃ H H H 6-Cl H W.416 B₃ F H H H 6-Cl H W.417 B₃ CN H H H 6-Cl H W.418 B₃ H CH₃ H H 6-Cl H W.419 B₃ CH₃ CH₃ H H 6-Cl H W.420 B₃ CH₂CH₃ CH₃ H H 6-Cl H W.421 B₃ F CH₃ H H 6-Cl H W.422 B₃ CN CH₃ H H 6-Cl H W.423 B₃ H CH₂CH₃ H H 6-Cl H W.424 B₃ CH₃ CH₂CH₃ H H 6-Cl H W.425 B₃ F CH₂CH₃ H H 6-Cl H W.426 B₃ CN CH₂CH₃ H H 6-Cl H W.427 B₃ H H F H 6-Cl H W.428 B₃ CH₃ H F H 6-Cl H W.429 B₃ F H F H 6-Cl H W.430 B₃ H CH₃ F H 6-Cl H W.431 B₃ CH₃ CH₃ F H 6-Cl H W.432 B₃ F CH₃ F H 6-Cl H W.433 B₃ H H F F 6-Cl H W.434 B₃ H H CH₃ CH₃ 6-Cl H W.435 B₃ F H CH₃ CH₃ 6-Cl H W.436 B₃ H CH₃ CH₃ CH₃ 6-Cl H W.437 B₃ CH₃ CH₃ CH₃ CH₃ 6-Cl H W.438 B₃ F CH₃ CH₃ CH₃ 6-Cl H W.439 B₃ H H H H 7-Cl H W.440 B₃ CH₃ H H H 7-Cl H W.441 B₃ CH₂CH₃ H H H 7-Cl H W.442 B₃ F H H H 7-Cl H W.443 B₃ CN H H H 7-Cl H W.444 B₃ H CH₃ H H 7-Cl H W.445 B₃ CH₃ CH₃ H H 7-Cl H W.446 B₃ CH₂CH₃ CH₃ H H 7-Cl H W.447 B₃ F CH₃ H H 7-Cl H W.448 B₃ CN CH₃ H H 7-Cl H W.449 B₃ H CH₂CH₃ H H 7-Cl H W.450 B₃ CH₃ CH₂CH₃ H H 7-Cl H W.451 B₃ F CH₂CH₃ H H 7-Cl H W.452 B₃ CN CH₂CH₃ H H 7-Cl H W.453 B₃ H H F H 7-Cl H W.454 B₃ CH₃ H F H 7-Cl H W.455 B₃ F H F H 7-Cl H W.456 B₃ H CH₃ F H 7-Cl H W.457 B₃ CH₃ CH₃ F H 7-Cl H W.458 B₃ F CH₃ F H 7-Cl H W.459 B₃ H H F F 7-Cl H W.460 B₃ H H CH₃ CH₃ 7-Cl H W.461 B₃ F H CH₃ CH₃ 7-Cl H W.462 B₃ H CH₃ CH₃ CH₃ 7-Cl H W.463 B₃ CH₃ CH₃ CH₃ CH₃ 7-Cl H W.464 B₃ F CH₃ CH₃ CH₃ 7-Cl H W.465 B₃ H H H H 8-Cl H W.466 B₃ CH₃ H H H 8-Cl H W.467 B₃ CH₂CH₃ H H H 8-Cl H W.468 B₃ F H H H 8-Cl H W.469 B₃ CN H H H 8-Cl H W.470 B₃ H CH₃ H H 8-Cl H W.471 B₃ CH₃ CH₃ H H 8-Cl H W.472 B₃ CH₂CH₃ CH₃ H H 8-Cl H W.473 B₃ F CH₃ H H 8-Cl H W.474 B₃ CN CH₃ H H 8-Cl H W.475 B₃ H CH₂CH₃ H H 8-Cl H W.476 B₃ CH₃ CH₂CH₃ H H 8-Cl H W.477 B₃ F CH₂CH₃ H H 8-Cl H W.478 B₃ CN CH₂CH₃ H H 8-Cl H W.479 B₃ H H F H 8-Cl H W.480 B₃ CH₃ H F H 8-Cl H W.481 B₃ F H F H 8-Cl H W.482 B₃ H CH₃ F H 8-Cl H W.483 B₃ CH₃ CH₃ F H 8-Cl H W.484 B₃ F CH₃ F H 8-Cl H W.485 B₃ H H F F 8-Cl H W.486 B₃ H H CH₃ CH₃ 8-Cl H W.487 B₃ F H CH₃ CH₃ 8-Cl H W.488 B₃ H CH₃ CH₃ CH₃ 8-Cl H W.489 B₃ CH₃ CH₃ CH₃ CH₃ 8-Cl H W.490 B₃ F CH₃ CH₃ CH₃ 8-Cl H W.491 B₃ H H H H 2-Cl 5-Cl W.492 B₃ CH₃ H H H 2-Cl 5-Cl W.493 B₃ CH₂CH₃ H H H 2-Cl 5-Cl W.494 B₃ F H H H 2-Cl 5-Cl W.495 B₃ CN H H H 2-Cl 5-Cl W.496 B₃ H CH₃ H H 2-Cl 5-Cl W.497 B₃ CH₃ CH₃ H H 2-Cl 5-Cl W.498 B₃ CH₂CH₃ CH₃ H H 2-Cl 5-Cl W.499 B₃ F CH₃ H H 2-Cl 5-Cl W.500 B₃ CN CH₃ H H 2-Cl 5-Cl W.501 B₃ H CH₂CH₃ H H 2-Cl 5-Cl W.502 B₃ CH₃ CH₂CH₃ H H 2-Cl 5-Cl W.503 B₃ F CH₂CH₃ H H 2-Cl 5-Cl W.504 B₃ CN CH₂CH₃ H H 2-Cl 5-Cl W.505 B₃ H H F H 2-Cl 5-Cl W.506 B₃ CH₃ H F H 2-Cl 5-Cl W.507 B₃ F H F H 2-Cl 5-Cl W.508 B₃ H CH₃ F H 2-Cl 5-Cl W.509 B₃ CH₃ CH₃ F H 2-Cl 5-Cl W.510 B₃ F CH₃ F H 2-Cl 5-Cl W.511 B₃ H H F F 2-Cl 5-Cl W.512 B₃ H H CH₃ CH₃ 2-Cl 5-Cl W.513 B₃ F H CH₃ CH₃ 2-Cl 5-Cl W.514 B₃ H CH₃ CH₃ CH₃ 2-Cl 5-Cl W.515 B₃ CH₃ CH₃ CH₃ CH₃ 2-Cl 5-Cl W.516 B₃ F CH₃ CH₃ CH₃ 2-Cl 6-Cl W.517 B₃ H H H H 2-Cl 6-Cl W.518 B₃ CH₃ H H H 2-Cl 6-Cl W.519 B₃ CH₂CH₃ H H H 2-Cl 6-Cl W.520 B₃ F H H H 2-Cl 6-Cl W.521 B₃ CN H H H 2-Cl 6-Cl W.522 B₃ H CH₃ H H 2-Cl 6-Cl W.523 B₃ CH₃ CH₃ H H 2-Cl 6-Cl W.524 B₃ CH₂CH₃ CH₃ H H 2-Cl 6-Cl W.525 B₃ F CH₃ H H 2-Cl 6-Cl W.526 B₃ CN CH₃ H H 2-Cl 6-Cl W.527 B₃ H CH₂CH₃ H H 2-Cl 6-Cl W.528 B₃ CH₃ CH₂CH₃ H H 2-Cl 6-Cl W.529 B₃ F CH₂CH₃ H H 2-Cl 6-Cl W.530 B₃ CN CH₂CH₃ H H 2-Cl 6-Cl W.531 B₃ H H F H 2-Cl 6-Cl W.532 B₃ CH₃ H F H 2-Cl 6-Cl W.533 B₃ F H F H 2-Cl 6-Cl W.534 B₃ H CH₃ F H 2-Cl 6-Cl W.535 B₃ CH₃ CH₃ F H 2-Cl 6-Cl W.536 B₃ F CH₃ F H 2-Cl 6-Cl W.537 B₃ H H F F 2-Cl 6-Cl W.538 B₃ H H CH₃ CH₃ 2-Cl 6-Cl W.539 B₃ F H CH₃ CH₃ 2-Cl 6-Cl W.540 B₃ H CH₃ CH₃ CH₃ 2-Cl 6-Cl W.541 B₃ CH₃ CH₃ CH₃ CH₃ 2-Cl 6-Cl W.542 B₃ F CH₃ CH₃ CH₃ 2-Cl 6-Cl 243 B₃ H H H H 2-Cl 7-Cl W.544 B₃ CH₃ H H H 2-Cl 7-Cl W.545 B₃ CH₂CH₃ H H H 2-Cl 7-Cl W.546 B₃ F H H H 2-Cl 7-Cl W.547 B₃ CN H H H 2-Cl 7-Cl W.548 B₃ H CH₃ H H 2-Cl 7-Cl W.549 B₃ CH₃ CH₃ H H 2-Cl 7-Cl W.550 B₃ CH₂CH₃ CH₃ H H 2-Cl 7-Cl W.551 B₃ F CH₃ H H 2-Cl 7-Cl W.552 B₃ CN CH₃ H H 2-Cl 7-Cl W.553 B₃ H CH₂CH₃ H H 2-Cl 7-Cl W.554 B₃ CH₃ CH₂CH₃ H H 2-Cl 7-Cl W.555 B₃ F CH₂CH₃ H H 2-Cl 7-Cl W.556 B₃ CN CH₂CH₃ H H 2-Cl 7-Cl W.557 B₃ H H F H 2-Cl 7-Cl W.558 B₃ CH₃ H F H 2-Cl 7-Cl W.559 B₃ F H F H 2-Cl 7-Cl W.560 B₃ H CH₃ F H 2-Cl 7-Cl W.561 B₃ CH₃ CH₃ F H 2-Cl 7-Cl W.562 B₃ F CH₃ F H 2-Cl 7-Cl W.563 B₃ H H F F 2-Cl 7-Cl W.564 B₃ H H CH₃ CH₃ 2-Cl 7-Cl W.565 B₃ F H CH₃ CH₃ 2-Cl 7-Cl W.566 B₃ H CH₃ CH₃ CH₃ 2-Cl 7-Cl W.567 B₃ CH₃ CH₃ CH₃ CH₃ 2-Cl 7-Cl W.568 B₃ F CH₃ CH₃ CH₃ 2-Cl 7-Cl W.569 B₃ H H H H 2-Cl 8-Cl W.570 B₃ CH₃ H H H 2-Cl 8-Cl W.571 B₃ CH₂CH₃ H H H 2-Cl 8-Cl W.572 B₃ F H H H 2-Cl 8-Cl W.573 B₃ CN H H H 2-Cl 8-Cl W.574 B₃ H CH₃ H H 2-Cl 8-Cl W.575 B₃ CH₃ CH₃ H H 2-Cl 8-Cl W.576 B₃ CH₂CH₃ CH₃ H H 2-Cl 8-Cl W.577 B₃ F CH₃ H H 2-Cl 8-Cl W.578 B₃ CN CH₃ H H 2-Cl 8-Cl W.579 B₃ H CH₂CH₃ H H 2-Cl 8-Cl W.580 B₃ CH₃ CH₂CH₃ H H 2-Cl 8-Cl W.581 B₃ F CH₂CH₃ H H 2-Cl 8-Cl W.582 B₃ CN CH₂CH₃ H H 2-Cl 8-Cl W.583 B₃ H H F H 2-Cl 8-Cl W.584 B₃ CH₃ H F H 2-Cl 8-Cl W.585 B₃ F H F H 2-Cl 8-Cl W.586 B₃ H CH₃ F H 2-Cl 8-Cl W.587 B₃ CH₃ CH₃ F H 2-Cl 8-Cl W.588 B₃ F CH₃ F H 2-Cl 8-Cl W.589 B₃ H H F F 2-Cl 8-Cl W.590 B₃ H H CH₃ CH₃ 2-Cl 8-Cl W.591 B₃ F H CH₃ CH₃ 2-Cl 8-Cl W.592 B₃ H CH₃ CH₃ CH₃ 2-Cl 8-Cl W.593 B₃ CH₃ CH₃ CH₃ CH₃ 2-Cl 8-Cl W.594 B₃ F CH₃ CH₃ CH₃ 2-Cl 8-Cl W.595 B₃ H H H H 6-p-Cl-phenyl 2-Cl W.596 B₃ CH₃ H H H 6-p-Cl-phenyl 2-Cl W.597 B₃ CH₂CH₃ H H H 6-p-Cl-phenyl 2-Cl W.598 B₃ F H H H 6-p-Cl-phenyl 2-Cl W.599 B₃ CN H H H 6-p-Cl-phenyl 2-Cl W.600 B₃ H CH₃ H H 6-p-Cl-phenyl 2-Cl W.601 B₃ CH₃ CH₃ H H 6-p-Cl-phenyl 2-Cl W.602 B₃ CH₂CH₃ CH₃ H H 6-p-Cl-phenyl 2-Cl W.603 B₃ F CH₃ H H 6-p-Cl-phenyl 2-Cl W.604 B₃ CN CH₃ H H 6-p-Cl-phenyl 2-Cl W.605 B₃ H CH₂CH₃ H H 6-p-Cl-phenyl 2-Cl W.606 B₃ CH₃ CH₂CH₃ H H 6-p-Cl-phenyl 2-Cl W.607 B₃ F CH₂CH₃ H H 6-p-Cl-phenyl 2-Cl W.608 B₃ CN CH₂CH₃ H H 6-p-Cl-phenyl 2-Cl W.609 B₃ H H F H 6-p-Cl-phenyl 2-Cl W.610 B₃ CH₃ H F H 6-p-Cl-phenyl 2-Cl W.611 B₃ F H F H 6-p-Cl-phenyl 2-Cl W.612 B₃ H CH₃ F H 6-p-Cl-phenyl 2-Cl W.613 B₃ CH₃ CH₃ F H 6-p-Cl-phenyl 2-Cl W.614 B₃ F CH₃ F H 6-p-Cl-phenyl 2-Cl W.615 B₃ H H F F 6-p-Cl-phenyl 2-Cl W.616 B₃ H H CH₃ CH₃ 6-p-Cl-phenyl 2-Cl W.617 B₄ H H H H 2-Cl H W.618 B₄ CH₃ H H H 2-Cl H W.619 B₄ CH₂CH₃ H H H 2-Cl H W.620 B₄ F H H H 2-Cl H W.621 B₄ CN H H H 2-Cl H W.622 B₄ H CH₃ H H 2-Cl H W.623 B₄ CH₃ CH₃ H H 2-Cl H W.624 B₄ CH₂CH₃ CH₃ H H 2-Cl H W.625 B₄ F CH₃ H H 2-Cl H W.626 B₄ CN CH₃ H H 2-Cl H W.627 B₄ H CH₂CH₃ H H 2-Cl H W.628 B₄ CH₃ CH₂CH₃ H H 2-Cl H W.629 B₄ F CH₂CH₃ H H 2-Cl H W.630 B₄ CN CH₂CH₃ H H 2-Cl H W.631 B₄ H H F H 2-Cl H W.632 B₄ CH₃ H F H 2-Cl H W.633 B₄ F H F H 2-Cl H W.634 B₄ H CH₃ F H 2-Cl H W.635 B₄ CH₃ CH₃ F H 2-Cl H W.636 B₄ F CH₃ F H 2-Cl H W.637 B₄ H H F F 2-Cl H W.638 B₄ H H CH₃ CH₃ 2-Cl H W.639 B₄ F H CH₃ CH₃ 2-Cl H W.640 B₄ H CH₃ CH₃ CH₃ 2-Cl H W.641 B₄ CH₃ CH₃ CH₃ CH₃ 2-Cl H W.642 B₄ F CH₃ CH₃ CH₃ 2-Cl H W.643 B₄ H H H H 4-Cl H W.644 B₄ CH₃ H H H 4-Cl H W.645 B₄ CH₂CH₃ H H H 4-Cl H W.646 B₄ F H H H 4-Cl H W.647 B₄ CN H H H 4-Cl H W.648 B₄ H CH₃ H H 4-Cl H W.649 B₄ CH₃ CH₃ H H 4-Cl H W.650 B₄ CH₂CH₃ CH₃ H H 4-Cl H W.651 B₄ F CH₃ H H 4-Cl H W.652 B₄ CN CH₃ H H 4-Cl H W.653 B₄ H CH₂CH₃ H H 4-Cl H W.654 B₄ CH₃ CH₂CH₃ H H 4-Cl H W.655 B₄ F CH₂CH₃ H H 4-Cl H W.656 B₄ CN CH₂CH₃ H H 4-Cl H W.657 B₄ H H F H 4-Cl H W.658 B₄ CH₃ H F H 4-Cl H W.659 B₄ F H F H 4-Cl H W.660 B₄ H CH₃ F H 4-Cl H W.661 B₄ CH₃ CH₃ F H 4-Cl H W.662 B₄ F CH₃ F H 4-Cl H W.663 B₄ H H F F 4-Cl H W.664 B₄ H H CH₃ CH₃ 4-Cl H W.665 B₄ F H CH₃ CH₃ 4-Cl H W.666 B₄ H CH₃ CH₃ CH₃ 4-Cl H W.667 B₄ CH₃ CH₃ CH₃ CH₃ 4-Cl H W.668 B₄ F CH₃ CH₃ CH₃ 4-Cl H W.669 B₄ H H H H 6-Cl H W.670 B₄ CH₃ H H H 6-Cl H W.671 B₄ CH₂CH₃ H H H 6-Cl H W.672 B₄ F H H H 6-Cl H W.673 B₄ CN H H H 6-Cl H W.674 B₄ H CH₃ H H 6-Cl H W.675 B₄ CH₃ CH₃ H H 6-Cl H W.676 B₄ CH₂CH₃ CH₃ H H 6-Cl H W.677 B₄ F CH₃ H H 6-Cl H W.678 B₄ CN CH₃ H H 6-Cl H W.679 B₄ H CH₂CH₃ H H 6-Cl H W.680 B₄ CH₃ CH₂CH₃ H H 6-Cl H W.681 B₄ F CH₂CH₃ H H 6-Cl H W.682 B₄ CN CH₂CH₃ H H 6-Cl H W.683 B₄ H H F H 6-Cl H W.684 B₄ CH₃ H F H 6-Cl H W.685 B₄ F H F H 6-Cl H W.686 B₄ H CH₃ F H 6-Cl H W.687 B₄ CH₃ CH₃ F H 6-Cl H W.688 B₄ F CH₃ F H 6-Cl H W.689 B₄ H H F F 6-Cl H W.690 B₄ H H CH₃ CH₃ 6-Cl H W.691 B₄ F H CH₃ CH₃ 6-Cl H W.692 B₄ H CH₃ CH₃ CH₃ 6-Cl H W.693 B₄ CH₃ CH₃ CH₃ CH₃ 6-Cl H W.694 B₄ F CH₃ CH₃ CH₃ 6-Cl H W.695 B₄ H H H H 7-Cl H W.696 B₄ CH₃ H H H 7-Cl H W.697 B₄ CH₂CH₃ H H H 7-Cl H W.698 B₄ F H H H 7-Cl H W.699 B₄ CN H H H 7-Cl H W.700 B₄ H CH₃ H H 7-Cl H W.701 B₄ CH₃ CH₃ H H 7-Cl H W.702 B₄ CH₂CH₃ CH₃ H H 7-Cl H W.703 B₄ F CH₃ H H 7-Cl H W.704 B₄ CN CH₃ H H 7-Cl H W.705 B₄ H CH₂CH₃ H H 7-Cl H W.706 B₄ CH₃ CH₂CH₃ H H 7-Cl H W.707 B₄ F CH₂CH₃ H H 7-Cl H W.708 B₄ CN CH₂CH₃ H H 7-Cl H W.709 B₄ H H F H 7-Cl H W.710 B₄ CH₃ H F H 7-Cl H W.711 B₄ F H F H 7-Cl H W.712 B₄ H CH₃ F H 7-Cl H W.713 B₄ CH₃ CH₃ F H 7-Cl H W.714 B₄ F CH₃ F H 7-Cl H W.715 B₄ H H F F 7-Cl H W.716 B₄ H H CH₃ CH₃ 7-Cl H W.717 B₄ F H CH₃ CH₃ 7-Cl H W.718 B₄ H CH₃ CH₃ CH₃ 7-Cl H W.719 B₄ CH₃ CH₃ CH₃ CH₃ 7-Cl H W.720 B₄ F CH₃ CH₃ CH₃ 7-Cl H W.721 B₄ H H H H 8-Cl H W.722 B₄ CH₃ H H H 8-Cl H W.723 B₄ CH₂CH₃ H H H 8-Cl H W.724 B₄ F H H H 8-Cl H W.725 B₄ CN H H H 8-Cl H W.726 B₄ H CH₃ H H 8-Cl H W.727 B₄ CH₃ CH₃ H H 8-Cl H W.728 B₄ CH₂CH₃ CH₃ H H 8-Cl H W.729 B₄ F CH₃ H H 8-Cl H W.730 B₄ CN CH₃ H H 8-Cl H W.731 B₄ H CH₂CH₃ H H 8-Cl H W.732 B₄ CH₃ CH₂CH₃ H H 8-Cl H W.733 B₄ F CH₂CH₃ H H 8-Cl H W.734 B₄ CN CH₂CH₃ H H 8-Cl H W.735 B₄ H H F H 8-Cl H W.736 B₄ CH₃ H F H 8-Cl H W.737 B₄ F H F H 8-Cl H W.738 B₄ H CH₃ F H 8-Cl H W.739 B₄ CH₃ CH₃ F H 8-Cl H W.740 B₄ F CH₃ F H 8-Cl H W.741 B₄ H H F F 8-Cl H W.742 B₄ H H CH₃ CH₃ 8-Cl H W.743 B₄ F H CH₃ CH₃ 8-Cl H W.744 B₄ H CH₃ CH₃ CH₃ 8-Cl H W.745 B₄ CH₃ CH₃ CH₃ CH₃ 8-Cl H W.746 B₄ F CH₃ CH₃ CH₃ 8-Cl H W.747 B₄ H H H H 2-Cl 5-Cl W.748 B₄ CH₃ H H H 2-Cl 5-Cl W.749 B₄ CH₂CH₃ H H H 2-Cl 5-Cl W.750 B₄ F H H H 2-Cl 5-Cl W.751 B₄ CN H H H 2-Cl 5-Cl W.752 B₄ H CH₃ H H 2-Cl 5-Cl W.753 B₄ CH₃ CH₃ H H 2-Cl 5-Cl W.754 B₄ CH₂CH₃ CH₃ H H 2-Cl 5-Cl W.755 B₄ F CH₃ H H 2-Cl 5-Cl W.756 B₄ CN CH₃ H H 2-Cl 5-Cl W.757 B₄ H CH₂CH₃ H H 2-Cl 5-Cl W.758 B₄ CH₃ CH₂CH₃ H H 2-Cl 5-Cl W.759 B₄ F CH₂CH₃ H H 2-Cl 5-Cl W.760 B₄ CN CH₂CH₃ H H 2-Cl 5-Cl W.761 B₄ H H F H 2-Cl 5-Cl W.762 B₄ CH₃ H F H 2-Cl 5-Cl W.763 B₄ F H F H 2-Cl 5-Cl W.764 B₄ H CH₃ F H 2-Cl 5-Cl W.765 B₄ CH₃ CH₃ F H 2-Cl 5-Cl W.766 B₄ F CH₃ F H 2-Cl 5-Cl W.767 B₄ H H F F 2-Cl 5-Cl W.768 B₄ H H CH₃ CH₃ 2-Cl 5-Cl W.769 B₄ F H CH₃ CH₃ 2-Cl 5-Cl W.770 B₄ H CH₃ CH₃ CH₃ 2-Cl 5-Cl W.771 B₄ CH₃ CH₃ CH₃ CH₃ 2-Cl 5-Cl W.772 B₄ F CH₃ CH₃ CH₃ 2-Cl 6-Cl W.773 B₄ H H H H 2-Cl 6-Cl W.774 B₄ CH₃ H H H 2-Cl 6-Cl W.775 B₄ CH₂CH₃ H H H 2-Cl 6-Cl W.776 B₄ F H H H 2-Cl 6-Cl W.777 B₄ CN H H H 2-Cl 6-Cl W.778 B₄ H CH₃ H H 2-Cl 6-Cl W.779 B₄ CH₃ CH₃ H H 2-Cl 6-Cl W.780 B₄ CH₂CH₃ CH₃ H H 2-Cl 6-Cl W.781 B₄ F CH₃ H H 2-Cl 6-Cl W.782 B₄ CN CH₃ H H 2-Cl 6-Cl W.783 B₄ H CH₂CH₃ H H 2-Cl 6-Cl W.784 B₄ CH₃ CH₂CH₃ H H 2-Cl 6-Cl W.785 B₄ F CH₂CH₃ H H 2-Cl 6-Cl W.786 B₄ CN CH₂CH₃ H H 2-Cl 6-Cl W.787 B₄ H H F H 2-Cl 6-Cl W.788 B₄ CH₃ H F H 2-Cl 6-Cl W.789 B₄ F H F H 2-Cl 6-Cl W.790 B₄ H CH₃ F H 2-Cl 6-Cl W.791 B₄ CH₃ CH₃ F H 2-Cl 6-Cl W.792 B₄ F CH₃ F H 2-Cl 6-Cl W.793 B₄ H H F F 2-Cl 6-Cl W.794 B₄ H H CH₃ CH₃ 2-Cl 6-Cl W.795 B₄ F H CH₃ CH₃ 2-Cl 6-Cl W.796 B₄ H CH₃ CH₃ CH₃ 2-Cl 6-Cl W.797 B₄ CH₃ CH₃ CH₃ CH₃ 2-Cl 6-Cl W.798 B₄ F CH₃ CH₃ CH₃ 2-Cl 6-Cl W.799 B₄ H H H H 2-Cl 7-Cl W.800 B₄ CH₃ H H H 2-Cl 7-Cl W.801 B₄ CH₂CH₃ H H H 2-Cl 7-Cl W.802 B₄ F H H H 2-Cl 7-Cl W.803 B₄ CN H H H 2-Cl 7-Cl W.804 B₄ H CH₃ H H 2-Cl 7-Cl W.805 B₄ CH₃ CH₃ H H 2-Cl 7-Cl W.806 B₄ CH₂CH₃ CH₃ H H 2-Cl 7-Cl W.807 B₄ F CH₃ H H 2-Cl 7-Cl W.808 B₄ CN CH₃ H H 2-Cl 7-Cl W.809 B₄ H CH₂CH₃ H H 2-Cl 7-Cl W.810 B₄ CH₃ CH₂CH₃ H H 2-Cl 7-Cl W.811 B₄ F CH₂CH₃ H H 2-Cl 7-Cl W.812 B₄ CN CH₂CH₃ H H 2-Cl 7-Cl W.813 B₄ H H F H 2-Cl 7-Cl W.814 B₄ CH₃ H F H 2-Cl 7-Cl W.815 B₄ F H F H 2-Cl 7-Cl W.816 B₄ H CH₃ F H 2-Cl 7-Cl W.817 B₄ CH₃ CH₃ F H 2-Cl 7-Cl W.818 B₄ F CH₃ F H 2-Cl 7-Cl W.819 B₄ H H F F 2-Cl 7-Cl W.820 B₄ H H CH₃ CH₃ 2-Cl 7-Cl W.821 B₄ F H CH₃ CH₃ 2-Cl 7-Cl W.822 B₄ H CH₃ CH₃ CH₃ 2-Cl 7-Cl W.823 B₄ CH₃ CH₃ CH₃ CH₃ 2-Cl 7-Cl W.824 B₄ F CH₃ CH₃ CH₃ 2-Cl 7-Cl W.825 B₄ H H H H 2-Cl 8-Cl W.826 B₄ CH₃ H H H 2-Cl 8-Cl W.827 B₄ CH₂CH₃ H H H 2-Cl 8-Cl W.828 B₄ F H H H 2-Cl 8-Cl W.829 B₄ CN H H H 2-Cl 8-Cl W.830 B₄ H CH₃ H H 2-Cl 8-Cl W.831 B₄ CH₃ CH₃ H H 2-Cl 8-Cl W.832 B₄ CH₂CH₃ CH₃ H H 2-Cl 8-Cl W.833 B₄ F CH₃ H H 2-Cl 8-Cl W.834 B₄ CN CH₃ H H 2-Cl 8-Cl W.835 B₄ H CH₂CH₃ H H 2-Cl 8-Cl W.836 B₄ CH₃ CH₂CH₃ H H 2-Cl 8-Cl W.837 B₄ F CH₂CH₃ H H 2-Cl 8-Cl W.838 B₄ CN CH₂CH₃ H H 2-Cl 8-Cl W.839 B₄ H H F H 2-Cl 8-Cl W.840 B₄ CH₃ H F H 2-Cl 8-Cl W.841 B₄ F H F H 2-Cl 8-Cl W.842 B₄ H CH₃ F H 2-Cl 8-Cl 243 B₄ CH₃ CH₃ F H 2-Cl 8-Cl W.844 B₄ F CH₃ F H 2-Cl 8-Cl W.845 B₄ H H F F 2-Cl 8-Cl W.846 B₄ H H CH₃ CH₃ 2-Cl 8-Cl W.847 B₄ F H CH₃ CH₃ 2-Cl 8-Cl W.848 B₄ H CH₃ CH₃ CH₃ 2-Cl 8-Cl W.849 B₄ CH₃ CH₃ CH₃ CH₃ 2-Cl 8-Cl W.850 B₄ F CH₃ CH₃ CH₃ 2-Cl 8-Cl W.851 B₄ H H H H 6-p-Cl-phenyl 2-Cl W.852 B₄ CH₃ H H H 6-p-Cl-phenyl 2-Cl W.853 B₄ CH₂CH₃ H H H 6-p-Cl-phenyl 2-Cl W.254 B₄ F H H H 6-p-Cl-phenyl 2-Cl W.855 B₄ CN H H H 6-p-Cl-phenyl 2-Cl W.856 B₄ H CH₃ H H 6-p-Cl-phenyl 2-Cl W.857 B₄ CH₃ CH₃ H H 6-p-Cl-phenyl 2-Cl W.858 B₄ CH₂CH₃ CH₃ H H 6-p-Cl-phenyl 2-Cl W.859 B₄ F CH₃ H H 6-p-Cl-phenyl 2-Cl W.860 B₄ CN CH₃ H H 6-p-Cl-phenyl 2-Cl W.861 B₄ H CH₂CH₃ H H 6-p-Cl-phenyl 2-Cl W.862 B₄ CH₃ CH₂CH₃ H H 6-p-Cl-phenyl 2-Cl W.863 B₄ F CH₂CH₃ H H 6-p-Cl-phenyl 2-Cl W.864 B₄ CN CH₂CH₃ H H 6-p-Cl-phenyl 2-Cl W.865 B₄ H H F H 6-p-Cl-phenyl 2-Cl W.866 B₄ CH₃ H F H 6-p-Cl-phenyl 2-Cl W.867 B₄ F H F H 6-p-Cl-phenyl 2-Cl W.868 B₄ H CH₃ F H 6-p-Cl-phenyl 2-Cl W.869 B₄ CH₃ CH₃ F H 6-p-Cl-phenyl 2-Cl W.870 B₄ F CH₃ F H 6-p-Cl-phenyl 2-Cl W.871 B₄ H H F F 6-p-Cl-phenyl 2-Cl W.872 B₄ H H CH₃ CH₃ 6-p-Cl-phenyl 2-Cl In Table W the group B stands for the group B₁, B₂, B₃ or B₄:

Table 9 provides 872 compounds of formula (IB), wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R₁, R₂, R₃, R₄, R_(9a) and R_(9b) are as defined in Table W. For example, compound 9.001 has the following structure:

Table 10 provides 872 compounds of formula (IB) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R₁, R₂, R₃, R₄, R_(9a) and R_(9b) are as defined in Table W.

Table 11 provides 872 compounds of formula (IB) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R₁, R₂, R₃, R₄, R_(9a) and R_(9b) are as defined in Table W.

Table 12 provides 872 compounds of formula (IB) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R₁, R₂, R₃, R₄, R_(9a) and R_(9b) are as defined in Table W.

Table 13 provides 872 compounds of formula (IB) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R₁, R₂, R₃, R₄, R_(9a) and R_(9b) are as defined in Table W.

Table 14 provides 872 compounds of formula (IB) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R₁, R₂, R₃, R₄, R_(9a) and R_(9b) are as defined in Table W.

Table 15 provides 872 compounds of formula (IB) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R₁, R₂, R₃, R₄, R_(9a) and R_(9b) are as defined in Table W.

Table 16 provides 872 compounds of formula (IB) wherein A is

wherein the broken lines indicate the point of attachment of the group A to the amide group, and B, R₁, R₂, R₃, R₄, R_(9a) and R_(9b) are as defined in Table W. Table 17: Compounds of Formula IIA

Illustrative of the compounds of formula (IIA) are the compounds listed in Table 17 below. Characterising data for these compounds are given in Table 18.

TABLE 17 (IIA)

Cpd No. R₁ R₂ R₃ R₄ R_(9a) R_(9b) R_(9c) Z1.001 H H H H 4-Cl H H Z1.002 CH₃ H H H 4-Cl H H Z1.003 CH₂CH₃ H H H 4-Cl H H Z1.004 F H H H 4-Cl H H Z1.005 CN H H H 4-Cl H H Z1.006 H CH₃ H H 4-Cl H H Z1.007 CH₃ CH₃ H H 4-Cl H H Z1.008 CH₂CH₃ CH₃ H H 4-Cl H H Z1.009 F CH₃ H H 4-Cl H H Z1.010 CN CH₃ H H 4-Cl H H Z1.011 H CH₂CH₃ H H 4-Cl H H Z1.012 CH₃ CH₂CH₃ H H 4-Cl H H Z1.013 F CH₂CH₃ H H 4-Cl H H Z1.014 CN CH₂CH₃ H H 4-Cl H H Z1.015 H H F H 4-Cl H H Z1.016 CH₃ H F H 4-Cl H H Z1.017 F H F H 4-Cl H H Z1.018 H CH₃ F H 4-Cl H H Z1.019 CH₃ CH₃ F H 4-Cl H H Z1.020 F CH₃ F H 4-Cl H H Z1.021 H H F F 4-Cl H H Z1.022 CH₃ H F F 4-Cl H H Z1.023 F H F F 4-Cl H H Z1.024 H CH₃ F F 4-Cl H H Z1.025 CH₃ CH₃ F F 4-Cl H H Z1.026 F CH₃ F F 4-Cl H H Z1.027 H H H H 4-CF₃ H H Z1.028 CH₃ H H H 4-CF₃ H H Z1.029 CH₂CH₃ H H H 4-CF₃ H H Z1.030 F H H H 4-CF₃ H H Z1.031 CN H H H 4-CF₃ H H Z1.032 H CH₃ H H 4-CF₃ H H Z1.033 CH₃ CH₃ H H 4-CF₃ H H Z1.034 CH₂CH₃ CH₃ H H 4-CF₃ H H Z1.035 F CH₃ H H 4-CF₃ H H Z1.036 CN CH₃ H H 4-CF₃ H H Z1.037 H CH₂CH₃ H H 4-CF₃ H H Z1.038 CH₃ CH₂CH₃ H H 4-CF₃ H H Z1.039 F CH₂CH₃ H H 4-CF₃ H H Z1.040 CN CH₂CH₃ H H 4-CF₃ H H Z1.041 H H F H 4-CF₃ H H Z1.042 CH₃ H F H 4-CF₃ H H Z1.043 F H F H 4-CF₃ H H Z1.044 H CH₃ F H 4-CF₃ H H Z1.045 CH₃ CH₃ F H 4-CF₃ H H Z1.046 F CH₃ F H 4-CF₃ H H Z1.047 H H F F 4-CF₃ H H Z1.048 CH₃ H F F 4-CF₃ H H Z1.049 F H F F 4-CF₃ H H Z1.050 H CH₃ F F 4-CF₃ H H Z1.051 CH₃ CH₃ F F 4-CF₃ H H Z1.052 F CH₃ F F 4-CF₃ H H Z1.053 H H H H 4-OCF₃ H H Z1.054 CH₃ H H H 4-OCF₃ H H Z1.055 CH₂CH₃ H H H 4-OCF₃ H H Z1.056 F H H H 4-OCF₃ H H Z1.057 CN H H H 4-OCF₃ H H Z1.058 H CH₃ H H 4-OCF₃ H H Z1.059 CH₃ CH₃ H H 4-OCF₃ H H Z1.060 CH₂CH₃ CH₃ H H 4-OCF₃ H H Z1.061 F CH₃ H H 4-OCF₃ H H Z1.062 CN CH₃ H H 4-OCF₃ H H Z1.063 H CH₂CH₃ H H 4-OCF₃ H H Z1.064 CH₃ CH₂CH₃ H H 4-OCF₃ H H Z1.065 F CH₂CH₃ H H 4-OCF₃ H H Z1.066 CN CH₂CH₃ H H 4-OCF₃ H H Z1.067 H H F H 4-OCF₃ H H Z1.068 CH₃ H F H 4-OCF₃ H H Z1.069 F H F H 4-OCF₃ H H Z1.070 H CH₃ F H 4-OCF₃ H H Z1.071 CH₃ CH₃ F H 4-OCF₃ H H Z1.072 F CH₃ F H 4-OCF₃ H H Z1.073 H H F F 4-OCF₃ H H Z1.074 CH₃ H F F 4-OCF₃ H H Z1.075 F H F F 4-OCF₃ H H Z1.076 H CH₃ F F 4-OCF₃ H H Z1.077 CH₃ CH₃ F F 4-OCF₃ H H Z1.078 F CH₃ F F 4-OCF₃ H H Z1.079 H H H H 4-F H H Z1.080 F H H H 4-F H H Z1.081 H CH₃ H H 4-F H H Z1.082 F CH₃ H H 4-F H H Z1.083 H CH₂CH₃ H H 4-F H H Z1.084 H H F H 4-F H H Z1.085 F H F H 4-F H H Z1.086 H CH₃ F H 4-F H H Z1.087 F CH₃ F H 4-F H H Z1.088 H H F F 4-F H H Z1.089 F H F F 4-F H H Z1.090 F CH₃ F F 4-F H H Z1.091 H H H H 4-p-Cl-phenyl H H Z1.092 CH₃ H H H 4-p-Cl-phenyl H H Z1.093 CH₂CH₃ H H H 4-p-Cl-phenyl H H Z1.094 F H H H 4-p-Cl-phenyl H H Z1.095 CN H H H 4-p-Cl-phenyl H H Z1.096 H CH₃ H H 4-p-Cl-phenyl H H Z1.097 CH₃ CH₃ H H 4-p-Cl-phenyl H H Z1.098 CH₂CH₃ CH₃ H H 4-p-Cl-phenyl H H Z1.099 F CH₃ H H 4-p-Cl-phenyl H H Z1.100 CN CH₃ H H 4-p-Cl-phenyl H H Z1.101 H CH₂CH₃ H H 4-p-Cl-phenyl H H Z1.102 CH₃ CH₂CH₃ H H 4-p-Cl-phenyl H H Z1.103 F CH₂CH₃ H H 4-p-Cl-phenyl H H Z1.104 CN CH₂CH₃ H H 4-p-Cl-phenyl H H Z1.105 H H F H 4-p-Cl-phenyl H H Z1.106 CH₃ H F H 4-p-Cl-phenyl H H Z1.107 F H F H 4-p-Cl-phenyl H H Z1.108 H CH₃ F H 4-p-Cl-phenyl H H Z1.109 CH₃ CH₃ F H 4-p-Cl-phenyl H H Z1.110 F CH₃ F H 4-p-Cl-phenyl H H Z1.111 H H F F 4-p-Cl-phenyl H H Z1.112 CH₃ H F F 4-p-Cl-phenyl H H Z1.113 F H F F 4-p-Cl-phenyl H H Z1.114 H CH₃ F F 4-p-Cl-phenyl H H Z1.115 CH₃ CH₃ F F 4-p-Cl-phenyl H H Z1.116 F CH₃ F F 4-p-Cl-phenyl H H Z1.117 H H H H 4-C≡CC(CH₃)₃ H H Z1.118 CH₃ H H H 4-C≡CC(CH₃)₃ H H Z1.119 CH₂CH₃ H H H 4-C≡CC(CH₃)₃ H H Z1.120 F H H H 4-C≡CC(CH₃)₃ H H Z1.121 CN H H H 4-C≡CC(CH₃)₃ H H Z1.122 H CH₃ H H 4-C≡CC(CH₃)₃ H H Z1.123 CH₃ CH₃ H H 4-C≡CC(CH₃)₃ H H Z1.124 CH₂CH₃ CH₃ H H 4-C≡CC(CH₃)₃ H H Z1.125 F CH₃ H H 4-C≡CC(CH₃)₃ H H Z1.126 CN CH₃ H H 4-C≡CC(CH₃)₃ H H Z1.127 H CH₂CH₃ H H 4-C≡CC(CH₃)₃ H H Z1.128 CH₃ CH₂CH₃ H H 4-C≡CC(CH₃)₃ H H Z1.129 F CH₂CH₃ H H 4-C≡CC(CH₃)₃ H H Z1.130 CN CH₂CH₃ H H 4-C≡CC(CH₃)₃ H H Z1.131 H H F H 4-C≡CC(CH₃)₃ H H Z1.132 H CH₃ F H 4-C≡CC(CH₃)₃ H H Z1.133 CH₃ CH₃ F H 4-C≡CC(CH₃)₃ H H Z1.134 F CH₃ F H 4-C≡CC(CH₃)₃ H H Z1.135 H H F F 4-C≡CC(CH₃)₃ H H Z1.136 CH₃ H F F 4-C≡CC(CH₃)₃ H H Z1.137 F H F F 4-C≡CC(CH₃)₃ H H Z1.138 H CH₃ F F 4-C≡CC(CH₃)₃ H H Z1.139 CH₃ CH₃ F F 4-C≡CC(CH₃)₃ H H Z1.140 F CH₃ F F 4-C≡CC(CH₃)₃ H H Z1.141 H H H H 4-C≡CC(CH₃)₃ H H Z1.142 CH₃ H H H 4-C≡CC(CH₃)₃ H H Z1.143 H H H H 4-Cl 2-Cl H Z1.144 CH₃ H H H 4-Cl 2-Cl H Z1.145 CH₂CH₃ H H H 4-Cl 2-Cl H Z1.146 F H H H 4-Cl 2-Cl H Z1.147 CN H H H 4-Cl 2-Cl H Z1.148 H CH₃ H H 4-Cl 2-Cl H Z1.149 CH₃ CH₃ H H 4-Cl 2-Cl H Z1.150 CH₂CH₃ CH₃ H H 4-Cl 2-Cl H Z1.151 F CH₃ H H 4-Cl 2-Cl H Z1.152 CN CH₃ H H 4-Cl 2-Cl H Z1.153 H CH₂CH₃ H H 4-Cl 2-Cl H Z1.154 CH₃ CH₂CH₃ H H 4-Cl 2-Cl H Z1.155 F CH₂CH₃ H H 4-Cl 2-Cl H Z1.156 CN CH₂CH₃ H H 4-Cl 2-Cl H Z1.157 H H F H 4-Cl 2-Cl H Z1.158 CH₃ H F H 4-Cl 2-Cl H Z1.159 F H F H 4-Cl 2-Cl H Z1.160 H CH₃ F H 4-Cl 2-Cl H Z1.161 CH₃ CH₃ F H 4-Cl 2-Cl H Z1.162 F CH₃ F H 4-Cl 2-Cl H Z1.163 H H F F 4-Cl 2-Cl H Z1.164 CH₃ H F F 4-Cl 2-Cl H Z1.165 F H F F 4-Cl 2-Cl H Z1.166 H CH₃ F F 4-Cl 2-Cl H Z1.167 CH₃ CH₃ F F 4-Cl 2-Cl H Z1.168 F CH₃ F F 4-Cl 2-Cl H Z1.169 H H H H 4-F 2-F H Z1.170 CH₃ H H H 4-F 2-F H Z1.171 CH₂CH₃ H H H 4-F 2-F H Z1.172 F H H H 4-F 2-F H Z1.173 CN H H H 4-F 2-F H Z1.174 H CH₃ H H 4-F 2-F H Z1.175 CH₃ CH₃ H H 4-F 2-F H Z1.176 CH₂CH₃ CH₃ H H 4-F 2-F H Z1.177 F CH₃ H H 4-F 2-F H Z1.178 CN CH₃ H H 4-F 2-F H Z1.179 H CH₂CH₃ H H 4-F 2-F H Z1.180 CH₃ CH₂CH₃ H H 4-F 2-F H Z1.181 F CH₂CH₃ H H 4-F 2-F H Z1.182 CN CH₂CH₃ H H 4-F 2-F H Z1.183 H H F H 4-F 2-F H Z1.184 CH₃ H F H 4-F 2-F H Z1.185 F H F H 4-F 2-F H Z1.186 H CH₃ F H 4-F 2-F H Z1.187 CH₃ CH₃ F H 4-F 2-F H Z1.188 F CH₃ F H 4-F 2-F H Z1.189 H H F F 4-F 2-F H Z1.190 CH₃ H F F 4-F 2-F H Z1.191 F H F F 4-F 2-F H Z1.192 H CH₃ F F 4-F 2-F H Z1.193 CH₃ CH₃ F F 4-F 2-F H Z1.194 F CH₃ F F 4-F 2-F H Z1.195 H H H H 4-Cl 2-F H Z1.196 CH₃ H H H 4-Cl 2-F H Z1.197 CH₂CH₃ H H H 4-Cl 2-F H Z1.198 F H H H 4-Cl 2-F H Z1.199 CN H H H 4-Cl 2-F H Z1.200 H CH₃ H H 4-Cl 2-F H Z1.201 CH₃ CH₃ H H 4-Cl 2-F H Z1.202 CH₂CH₃ CH₃ H H 4-Cl 2-F H Z1.203 F CH₃ H H 4-Cl 2-F H Z1.204 CN CH₃ H H 4-Cl 2-F H Z1.205 H CH₂CH₃ H H 4-Cl 2-F H Z1.206 CH₃ CH₂CH₃ H H 4-Cl 2-F H Z1.207 F CH₂CH₃ H H 4-Cl 2-F H Z1.208 CN CH₂CH₃ H H 4-Cl 2-F H Z1.209 H H F H 4-Cl 2-F H Z1.210 CH₃ H F H 4-Cl 2-F H Z1.211 F H F H 4-Cl 2-F H Z1.212 H CH₃ F H 4-Cl 2-F H Z1.213 CH₃ CH₃ F H 4-Cl 2-F H Z1.214 F CH₃ F H 4-Cl 2-F H Z1.215 H H F F 4-Cl 2-F H Z1.216 CH₃ H F F 4-Cl 2-F H Z1.217 F H F F 4-Cl 2-F H Z1.218 H CH₃ F F 4-Cl 2-F H Z1.219 CH₃ CH₃ F F 4-Cl 2-F H Z1.220 F CH₃ F F 4-Cl 2-F H Z1.221 H H H H 4-F 2-Cl H Z1.222 H H H H 2-Cl H H Z1.223 CH₂CH₃ H H H 4-F 2-Cl H Z1.224 F H H H 4-F 2-Cl H Z1.225 CN H H H 4-F 2-Cl H Z1.226 H CH₃ H H 4-F 2-Cl H Z1.227 CH₃ CH₃ H H 4-F 2-Cl H Z1.228 CH₂CH₃ CH₃ H H 4-F 2-Cl H Z1.229 F CH₃ H H 4-F 2-Cl H Z1.230 CN CH₃ H H 4-F 2-Cl H Z1.231 H CH₂CH₃ H H 4-F 2-Cl H Z1.232 CH₃ CH₂CH₃ H H 4-F 2-Cl H Z1.233 F CH₂CH₃ H H 4-F 2-Cl H Z1.234 CN CH₂CH₃ H H 4-F 2-Cl H Z1.235 H H F H 4-F 2-Cl H Z1.236 CH₃ H F H 4-F 2-Cl H Z1.237 F H F H 4-F 2-Cl H Z1.238 H CH₃ F H 4-F 2-Cl H Z1.239 CH₃ CH₃ F H 4-F 2-Cl H Z1.240 F CH₃ F H 4-F 2-Cl H Z1.241 H H F F 4-F 2-Cl H Z1.242 CH₃ H F F 4-F 2-Cl H Z1.243 F H F F 4-F 2-Cl H Z1.244 H CH₃ F F 4-F 2-Cl H Z1.245 CH₃ CH₃ F F 4-F 2-Cl H Z1.246 F CH₃ F F 4-F 2-Cl H Z1.247 H H H H 4-p-Cl-phenyl 2-Cl H Z1.248 F H H H 4-p-Cl-phenyl 2-Cl H Z1.249 H CH₃ H H 4-p-Cl-phenyl 2-Cl H Z1.250 F CH₃ H H 4-p-Cl-phenyl 2-Cl H Z1.251 H H F H 4-p-Cl-phenyl 2-Cl H Z1.252 F H F H 4-p-Cl-phenyl 2-Cl H Z1.253 H CH₃ F H 4-p-Cl-phenyl 2-Cl H Z1.254 F CH₃ F H 4-p-Cl-phenyl 2-Cl H Z1.255 H H F F 4-p-Cl-phenyl 2-Cl H Z1.256 H CH₃ F F 4-p-Cl-phenyl 2-Cl H Z1.257 H H H H 4-Br 2-Cl H Z1.258 H H H H 4-Br 2-Cl 6-Cl Z1.259 H H H H 4-Cl 2-Cl 6-Cl Z1.260 H H H H 4-p-CF₃-phenyl 2-Cl 6-Cl Z1.261 H H H H 4-p-CF₃-phenyl 2-Cl H Z1.262 H H H H 4-(3′,4′-Cl₂)-phenyl 2-Cl H Z1.263 H H H H 4-(3′,4′-Cl₂)-phenyl 2-Cl 6-Cl Z1.264 H H H H 4-p-Cl-phenyl 2-Cl 6-Cl Z1.265 H H H H 4-(CH₃) 2-Cl 6-(CH₃) Z1.266 H H H H 4-(CH₃) 2-CH₃ 6-(CH₃) Z1.267 H H H H 4-C≡CC(CH₃)₃ 2-Cl H Z1.268 H H H H 4-C≡CC(CH₃)₃ 2-Cl 6-Cl Z1.269 H H H H 4-C≡CCH(CH₂)₂ 2-Cl H Z1.270 H H H H 4-C≡CCH(CH₂)₂ 2-Cl 6-Cl Z1.271 H H H H 4-CH═N—OCH₃ 2-Cl H Z1.272 H H H H 4-CH═N—OCH₃ 2-Cl 6-Cl Z1.273 H H H H 4-C(CH₃)═N—OCH₃ 2-Cl H Z1.274 H H H H 4-C(CH₃)═N—OCH₃ 2-Cl 6-Cl Table 18: Characterising Data

Table 18 shows selected melting point and selected NMR data for compounds of Tables 1 to 17. CDCl₃ was used as the solvent for NMR measurements, unless otherwise stated. If a mixture of solvents was present, this is indicated as, for example: CDCl₃/d₆-DMSO). No attempt is made to list all characterising data in all cases.

In Table 18 and throughout the description that follows, temperatures are given in degrees Celsius; “NMR” means nuclear magnetic resonance spectrum; MS stands for mass spectrum; “%” is percent by weight, unless corresponding concentrations are indicated in other units. The following abbreviations are used throughout this description:

-   -   m.p.=melting point b.p.=boiling point.     -   S=singlet br=broad     -   d=doublet dd=doublet of doublets     -   t=triplet q=quartet     -   m=multiplet ppm=parts per million

Compound No. 1H-NMR data: ppm (multiplicity/number of Hs) MS [M + H]⁺ m.p. (° C.) 1.001 (cis) 1.06-1.17 (m, 1H, CHH), 1.44 (q, 1H, CHH), 326/328 127 2.32-2.38 (q, 1H, CHAr), 3.23-3.29 (m, 1H, CHN), 3.73 (s, 3H, NCH₃), 6.08 (s, 1H, NH), 6.48-6.75 (t, 1H, CHF₂), 7.14-7.17 (d, 2H, Ar-H), 7.20-7.23 (d, 2H, Ar-H), 7.70 (s, 1H, Pyrazol-H) 1.004 Cis isomer: 1.50δ (m; 1H): 1.92δ (ddd; 1H): — — cis/trans = 7:3 3.62δ (m; 1H): 3.85δ (s; 3H): 6.05δ (br-s; 1H): 6.60δ (t; 1H) 7.30δ-7.40δ (m; 4H): 7.80δ (s; 1H). Trans isomer: 1.57δ (m; 1H): 1.67δ (ddd; 1H): 3.32δ (m; 1H): 6.70δ (br-s; 1H): 6.85δ (t; 1H): 7.30δ-7.40δ (m; 4H): 7.95δ (s; 1H). 1.079 (cis) 1.05δ (m; 1H): 1.42δ (m; 1H): 2.37δ (m; 1H): 310 — 3.25δ (m; 1H): 3.85δ (s; 3H): 6.00δ (br s; 1H): 6.57δ (t; 1H): 6.97δ-7.22δ (m; 4H): 7.77δ (s; 1H) 1.143 (cis) 1.15δ (m; 1H): 1.55δ (m; 1H): 2.42δ (m; 1H): 358/360/362 — 3.37δ (m; 1H): 3.85δ (s; 3H): 5.90δ (br s; 1H): 6.50δ (t; 1H): 7.42δ-7.10δ (m; 3H): 7.80δ (s; 1H) 1.222 (cis) 1.17δ (m; 1H): 1.50δ (m; 1H): 2.47δ (m; 1H): 326/328 — 3.37δ (m; 1H): 3.85δ (s; 3H): 5.90δ (br s; 1H): 6.45δ (t; 1H): 7.15δ-7.40δ (m; 4H): 7.77δ (s; 1H) 2.079 (cis) 1.05δ (m; 1H): 1.42δ (m; 1H): 2.40δ (m; 1H): 328 — 3.27δ (m; 1H): 3.90δ (s; 3H): 5.65δ (br s; 1H): 6.97δ-7.22δ (m; 4H): 7.80δ (s; 1H) 2.143 (cs) 1.15δ (m; 1H): 1.55δ (m; 1H): 2.40δ (m; 1H): 376/378/380 — 3.35δ (m; 1H): 3.90δ (s; 3H): 5.65δ (br s; 1H): 7.10δ-7.45δ (m; 3H): 7.82δ (s; 1H) 2.222 (cis) 1.15δ (m; 1H): 1.55δ (m; 1H): 2.45δ (m; 1H): 344/346 — 3.35δ (m; 1H): 3.87δ (s; 3H): 5.65δ (br s; 1H): 7.10δ-7.45δ (m; 4H): 7.80δ (s; 1H) 6.004 (cis) 1.60δ (m; 1H): 1.97δ (ddd; 1H): 3.67δ (m; 1H): 358 204-206 5.40δ (br-s; 1H): 7.10δ-7.65δ (m; 8H) 6.079 (cis) 1.10δ (m; 1H): 1.45δ (m; 1H): 2.40δ (m; 1H): 324 — 3.30δ (m; 1H): 5.40δ (br s; 1H): 6.97δ-7.60δ (m; 8H) 6.143 (cis) 1.25δ (m; 1H): 1.60δ (m; 1H): 2.54δ (m; 1H): 372/374/376 — 3.37δ (m; 1H): 5.35δ (br s; 1H): 7.10δ-7.60δ m; 7H): 6.222 (cis) 1.25δ (m; 1H): 1.60δ (m; 1H): 2.50δ (m; 1H): 340/342 — 3.47δ (m; 1H): 5.35δ (br s; 1H): 7.17δ-7.60δ (m; 8H) Z1.004 cis isomer: 1.15δ (ddd; 1H): 1.60δ (ddd; 1H): — — cis/trans = 7:3 3.10δ (ddd; 1H): 7.30δ-7.45δ (m; 4H). trans isomer: 1.27δ (ddd; 1H): 1.40δ (m; 1H): 2.57δ (ddd; 1H): 7.10δ-7.30δ (m; 4H).

FORMULATION EXAMPLES FOR COMPOUNDS OF FORMULA I Example F-1.1 to F-1.2 Emulsifiable Concentrates

Components F-1.1 F-1.2 compound of Tables 1 to 16 25% 50% calcium dodecylbenzenesulfonate  5%  6% castor oil polyethylene glycol ether  5% — (36 mol ethylenoxy units) tributylphenolpolyethylene glycol ether —  4% (30 mol ethylenoxy units) cyclohexanone — 20% xylene mixture 65% 20%

Emulsions of any desired concentration can be prepared by diluting such concentrates with water.

Example F-2 Emulsifiable Concentrate

Components F-2 compound of Tables 1 to 16 10% octylphenolpolyethylene glycol ether 3% (4 to 5 mol ethylenoxy units) calcium dodecylbenzenesulfonate 3% castor oil polyglycol ether 4% (36 mol ethylenoxy units) cyclohexanone 30% xylene mixture 50%

Emulsions of any desired concentration can be prepared by diluting such concentrates with water.

Examples F-3.1 to F-3.4 Solutions

Components F-3.1 F-3.2 F-3.3 F-3.4 compound of Tables 1 to 16 80% 10% 5% 95% propylene glycol monomethyl ether 20% — — — polyethylene glycol (relative molecular — 70% — — mass: 400 atomic mass units) N-methylpyrrolid-2-one — 20% — — epoxidised coconut oil — — 1%  5% benzin (boiling range: 160-190°) — — 94%  —

The solutions are suitable for use in the form of microdrops.

Examples F-4.1 to F-4.4 Granulates

Components F-4.1 F-4.2 F-4.3 F-4.4 compound of Tables 1 to 16 5% 10%  8% 21% kaolin 94%  — 79% 54% highly dispersed silicic acid 1% — 13%  7% attapulgite — 90% — 18%

The novel compound is dissolved in dichloromethane, the solution is sprayed onto the carrier and the solvent is then removed by distillation under vacuum.

Examples F-5.1 and F-5.2 Dusts

Components F-5.1 F-5.2 compound of Tables 1 to 16 2% 5% highly dispersed silicic acid 1% 5% talcum 97%  — kaolin — 90% 

Ready for use dusts are obtained by intimately mixing all components.

Examples F-6.1 to F-6.3 Wettable Powders

Components F-6.1 F-6.2 F-6.3 compound of Tables 1 to 16 25%  50% 75% sodium lignin sulfonate 5%  5% — sodium lauryl sulfate 3% —  5% sodium diisobutylnaphthalene sulfonate —  6% 10% octylphenolpolyethylene glycol ether —  2% — (7 to 8 mol ethylenoxy units) highly dispersed silicic acid 5% 10% 10% kaolin 62%  27% —

All components are mixed and the mixture is thoroughly ground in a suitable mill to give wettable powders which can be diluted with water to suspensions of any desired concentration.

Example F7 Flowable Concentrate for Seed Treatment

compound of Tables 1 to 16 40%  propylene glycol 5% copolymer butanol PO/EO 2% tristyrenephenole with 10-20 moles EO 2% 1,2-benzisothiazolin-3-one (in the form of a 20% solution in 0.5%   water) monoazo-pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in water) 0.2%   Water 45.3%  

The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.

BIOLOGICAL EXAMPLES Fungicidal Actions Example B-1 Action Against Podosohaera leucotricha/Apple (Powdery Mildew on Apple)

5 week old apple seedlings cv. McIntosh are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application apple plants are inoculated by shaking plants infected with apple powdery mildew above the test plants. After an incubation period of 12 days at 22° C. and 60% r.h. under a light regime of 14/10 hours (light/dark) the disease incidence is assessed. Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Example B-2 Action Against Venturia inaegualis/Apple (Scab on Apple)

4 week old apple seedlings cv. McIntosh are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application apple plants are inoculated by spraying a spore suspension (4×10⁵ conidia/ml) on the test plants. After an incubation period of 4 days at 21° C. and 95% r.h. the plants are placed for 4 days at 21° C. and 60% r.h. in a greenhouse. After another 4 day incubation period at 21° C. and 95% r.h. the disease incidence is assessed. Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Example B-3 Action Against Erysiphe graminis/Barley (Powdery Mildew on Barley)

1 week old barley plants cv. Express are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application barley plants are inoculated by shaking powdery mildew infected plants above the test plants. After an incubation period of 6 days at 20° C./18° C. (day/night) and 60% r. h. in a greenhouse the disease incidence is assessed. Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Example B-4 Action Against Botrytis cinerea/Apple (Botrytis on Apple Fruits)

In an apple fruit cv. Golden Delicious 3 holes are drilled and each filled with 3011 droplets of the formulated test compound (0.02% active ingredient). Two hours after application 50 μl of a spore suspension of B. cinerea (4×10⁵ conidia/ml) are pipetted on the application sites. After an incubation period of 7 days at 22° C. in a growth chamber the disease incidence is assessed. Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Example B-5 Action Against Botrytis cinerea/Grape (Botrytis on Grapes)

5 week old grape seedlings cv. Gutedel are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application grape plants are inoculated by spraying a spore suspension (1×10⁶ conidia/ml) on the test plants. After an incubation period of 4 days at 21° C. and 95% r.h. in a greenhouse the disease incidence is assessed. Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Example B-6 Action Against Botrytis cinerea/Tomato (Botrytis on Tomatoes)

4 week old tomato plants cv. Roter Gnom are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application tomato plants are inoculated by spraying a spore suspension (1×10⁵ conidia/ml) on the test plants. After an incubation period of 4 days at 20° C. and 95% r.h. in a growth chamber the disease incidence is assessed. Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Example B-7 Action Against Pyrenophora teres/Barley (Net Blotch on Barley)

1 week old barley plants cv. Express are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application barley plants are inoculated by spraying a spore suspension (3×10⁴ conidia/ml) on the test plants. After an incubation period of 2 days at 20° C. and 95% r.h. plants are kept for 2 days at 20° C. and 60% r.h. in a greenhouse. The disease incidence is assessed 4 days after inoculation. Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Example B-8 Action Against Septoria tritici/Wheat (Septoria Leaf Spot on Wheat)

2 week old wheat plants cv. Riband are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application, wheat plants are inoculated by spraying a spore suspension (10×10⁵ conidia/ml) on the test plants. After an incubation period of 1 day at 23° C. and 95% r.h., the plants are kept for 16 days at 23° C. and 60% r.h. in a greenhouse. The disease incidence is assessed 18 days after inoculation.

Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Example B-9 Action Against Uncinula necator/Grape (Powdery Mildew on Grape)

5 week old grape seedlings cv. Gutedel are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application, the grape plants are inoculated by shaking plants infected with grape powdery mildew above the test plants. After an incubation period of 7 days at 26° C. and 60% r.h. under a light regime of 14/10 hours (light/dark) the disease incidence is assessed. Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation).

Example B-10 Action Against Alternaria solani/Tomato (Early Blight on Tomatoes)

4 week old tomato plants cv. Roter Gnom are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. Two days after application, the tomato plants are inoculated by spraying a spore suspension (2×10⁵ conidia/ml) on the test plants. After an incubation period of 3 days at 20° C. and 95% r.h. in a growth chamber the disease incidence is assessed. Compounds 1.001, 1.004, 1.079, 1.143, 1.222, 2.079, 2.143. 2.222, 6.004, 6.079, 6.143 and 6.222 show good activity in this test (<20% infestation). 

What is claimed is:
 1. A fungicidally active compound having formula I:

wherein X is oxygen or sulfur; R₁ is hydrogen, halogen or C₁-C₆alkyl; R₂, R₃, R₄ and R₅ are each hydrogen; A is A₁

in which R₁₆ is C₁-C₄alkyl or C₁-C₄halogenalkyl; R₁₇ is C₁-C₄alkyl; and R₁₈ is hydrogen or halogen; and B is B₁

in which R_(19b) and R_(19d) are both hydrogen; and R_(19a), R_(19c) and R_(19e) are each independently hydrogen, halogen, cyano, C₂-C₆alkynyl, C₁-C₆halogenalkyl, C₁-C₆halogenalkoxy or phenyl, which is substituted halogen, provided that at least one of R_(19a), R_(19c) and R_(19e) is not hydrogen; and tautomers/isomers/enantiomers of the fungicidally active compound.
 2. A compound according to claim 1, wherein X is oxygen.
 3. A compound according to claim 1, wherein R_(19a) and R_(19e) are each independently hydrogen; and R_(19c) is a chloro group.
 4. A compound according to claim 1, wherein R₁ is hydrogen.
 5. A compound according to claim 3, wherein R₁ is hydrogen.
 6. A fungicidally active composition for controlling and protecting plants against phytopathogenic microorganisms, said fungicidally active composition comprising the fungicidally active compound of claim 1 and an inert carrier.
 7. A fungicidally active composition according to claim 6, further comprising at least one additional compound selected from fertilizers, micronutrient donors, herbicides, insecticides, fungicides, bactericides, nematicides, or molluscicides.
 8. A fungicidally active composition for controlling and protecting plants against phytopathogenic microorganisms, said fungicidally active composition comprising the fungicidally active compound of claim 2 and an inert carrier.
 9. A method of controlling or preventing infestation of useful plants by phytopathogenic microorganisms, wherein the fungicidally active compound of claim 1 or a composition comprising the fungicidally active compound as an active ingredient is applied to the plants, to parts thereof or a locus thereof. 